Efficacy and Safety of Intravenous-to-oral Lefamulin, a Pleuromutilin Antibiotic, for the Treatment of Community-acquired Bacterial Pneumonia: The Phase III Lefamulin Evaluation Against Pneumonia (LEAP 1) Trial.
Aged; Humans; Male; Adult; Female; Middle Aged; Double-Blind Method; Administration Intravenous; Microbial Sensitivity Tests; pneumonia; Randomized Controlled Trials as Topic; antibiotic; lefamulin; moxifloxacin; pleuromutilin; Anti-Bacterial Agents/administration & dosage/adverse effects/therapeutic use; Diterpenes/administration & dosage/adverse effects/therapeutic use; Linezolid/adverse effects/therapeutic use; Moxifloxacin/administration & dosage/adverse effects/therapeutic use; Pneumonia Bacterial/drug therapy/metabolism; Polycyclic Compounds/administration & dosage/adverse effects/therapeutic use; Thioglycolates/administration & dosage/adverse effects/therapeutic use
BACKGROUND: Lefamulin, a pleuromutilin antibiotic, is active against pathogens commonly causing community-acquired bacterial pneumonia (CABP). The Lefamulin Evaluation Against Pneumonia (LEAP 1) study was a global noninferiority trial to evaluate the efficacy and safety of lefamulin for the treatment of CABP. METHODS: In this double-blind study, adults with CABP of Pneumonia Outcomes Research Team risk class ≥III were randomized 1:1 to receive lefamulin at 150 mg intravenously (IV) every 12 hours or moxifloxacin at 400 mg IV every 24 hours. After 6 doses, patients could be switched to an oral study drug if prespecified improvement criteria were met. If methicillin-resistant Staphylococcus aureus was suspected, either linezolid or placebo was added to moxifloxacin or lefamulin, respectively. The US Food and Drug Administration primary endpoint was an early clinical response (ECR) 96 ± 24 hours after the first dose of the study drug in the intent-to-treat (ITT) population (noninferiority margin, 12.5%). The European Medicines Agency co-primary endpoints were an investigator assessment of clinical response (IACR) 5-10 days after the last dose of the study drug in the modified ITT (mITT) and clinically evaluable (CE) populations (noninferiority margin, 10%). RESULTS: There were 551 patients randomized (n = 276 lefamulin; n = 275 moxifloxacin). Lefamulin was noninferior to moxifloxacin for ECR (87.3% vs 90.2%, respectively; difference -2.9%, 95% confidence interval [CI] g -8.5 to 2.8) and IACR (mITT, 81.7% vs 84.2%, respectively; difference -2.6%, 95% CI -8.9 to 3.9; CE, 86.9% vs 89.4%, respectively; difference -2.5%, 95% CI -8.4 to 3.4). Rates of study drug discontinuation due to treatment-emergent adverse events were 2.9% for lefamulin and 4.4% for moxifloxacin. CONCLUSIONS: Lefamulin was noninferior to moxifloxacin for the primary efficacy endpoints and was generally safe and well tolerated. CLINICAL TRIALS REGISTRATION: NCT02559310.
File TM; Goldberg L; Das A; Sweeney C; Saviski J; Gelone SP; Seltzer E; Paukner S; Wicha WW; Talbot GH; Gasink LB
Clinical Infectious Diseases
2019
2019-11-13
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1093/cid/ciz090" target="_blank" rel="noreferrer noopener">10.1093/cid/ciz090</a>
Antipsychotic effects of verapamil in schizophrenia.
Adult; Female; Humans; Male; Middle Aged; Random Allocation; Double-Blind Method; Clinical Trials as Topic; Haloperidol/therapeutic use; Schizophrenia/*drug therapy; Verapamil/*therapeutic use
The antipsychotic effects of verapamil were tested in a double-blind, placebo-controlled, randomized study in 18 patients who met Research Diagnostic Criteria for acute schizophrenia. The antipsychotic effect of verapamil as measured by the Bunney-Hamburg Global Rating Scale were equal to those of haloperidol. Both verapamil and haloperidol were superior to placebo in decreasing psychotic symptoms. The results indicate that verapamil may have clinical utility in the treatment of schizophrenia.
Price W A
The Hillside journal of clinical psychiatry
1987
1987
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Randomized comparison of gastric pH control with intermittent and continuous intravenous infusion of famotidine in ICU patients.
Female; Humans; Male; Middle Aged; Aged; Treatment Outcome; Prospective Studies; Analysis of Variance; Double-Blind Method; Hydrogen-Ion Concentration; Intensive Care Units; Drug Administration Schedule; Famotidine/administration & dosage/*therapeutic use; Stomach Ulcer/blood/etiology/*prevention & control; Stomach/*drug effects/physiopathology; Infusions; Intravenous
OBJECTIVE: To compare gastric pH control using intravenous famotidine as a primed, continuous infusion versus intermittent infusion. METHODS: In a prospective, double-blind study, 40 ICU patients at risk for stress ulceration were randomly assigned to receive either famotidine 20 mg intravenous bolus followed by 1.67 mg/h infusion or famotidine 20 mg intravenously every 12 h. Intraluminal gastric pH was recorded at baseline and every 4 h using a glass electrode. Clinical outcome indicators were also monitored. Subjects were studied for a minimum of 24 h and a maximum of 6 days. Continuous variables were analyzed by ANOVA and nominal variables by Fisher's exact test (alpha = 0.05). RESULTS: Nineteen patients were randomized to the continuous infusion group, and 21 were randomized to the intermittent group. Using gastric pH greater than 4.0 as an endpoint, the continuous group exhibited better pH control, both in terms of percentage of total measurements (83% versus 63%, p \textless 0.001) and time spent above pH 4.0 (91% versus 76%, p \textless 0.01). Similar results were found at pH greater than 5.0 (78% versus 56% for all measurements for the continuous and bolus groups, respectively (p \textless 0.001), and 88% versus 72% for the time spent above pH 5.0 (p \textless 0.01). Clinical outcomes, including evidence for gastrointestinal bleeding and hospital mortality, did not differ significantly between groups. CONCLUSION: Famotidine infusion at 1.67 mg/h, when preceded by a bolus dose of 20 mg, provides a greater and more sustained increase in gastric pH than intermittent administration of famotidine 20 mg every 12 h.
Heiselman D E; Hulisz D T; Fricker R; Bredle D L; Black L D
The American journal of gastroenterology
1995
1995-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Clonidine in the treatment of premenstrual syndrome: a subgroup study.
Adult; Female; Humans; Double-Blind Method; Clinical Trials as Topic; Psychiatric Status Rating Scales; Placebos; beta-Endorphin/blood; Clonidine/*therapeutic use; Premenstrual Syndrome/blood/*drug therapy/psychology
The authors studied the effects of clonidine on a subgroup of women who had symptoms associated with premenstrual syndrome; the subgroup comprised 24 women aged 19 to 41 years who had "moderate" to "severe" cyclic decreases in beta-endorphin levels. All of the women received clonidine and placebo in a double-blind cross-over design that spanned four menstrual cycles. Clonidine was significantly (p less than .05) more effective than placebo in reducing symptoms.
Giannini A J; Sullivan B; Sarachene J; Loiselle R H
The Journal of clinical psychiatry
1988
1988-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Bromocriptine therapy in cocaine withdrawal.
Adult; Humans; Male; Random Allocation; Double-Blind Method; Clinical Trials as Topic; Psychiatric Status Rating Scales; *Cocaine; Bromocriptine/*therapeutic use; Substance Withdrawal Syndrome/*drug therapy/psychology
Twenty-four cocaine addicts who experienced withdrawal symptoms were studied for six weeks in a double-blind design. Half of the group received daily treatment with bromocriptine and the other half with placebo. Significant relief with bromocriptine was seen almost immediately and continued throughout the detoxification period. The authors speculate that the results are consistent with the "dopamine-depletion model" of cocaine withdrawal.
Giannini A J; Baumgartel P; DiMarzio L R
Journal of clinical pharmacology
1987
1987-04
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<a href="http://doi.org/10.1002/j.1552-4604.1987.tb03011.x" target="_blank" rel="noreferrer noopener">10.1002/j.1552-4604.1987.tb03011.x</a>
Mechanical Ventilation Antioxidant Trial.
Adult; Female; Humans; Male; Middle Aged; Time Factors; Aged; Length of Stay; Treatment Outcome; Prospective Studies; Oxidative Stress; Double-Blind Method; Intensive Care Units; Antioxidants/*therapeutic use; Antioxidants; Oxidative Stress/*drug effects; Critical Care/*methods; Human; Chi Square Test; Funding Source; Data Analysis Software; Middle Age; T-Tests; Ascorbic Acid/therapeutic use; Critical Illness; Cystine/analogs & derivatives/therapeutic use; Inflammation/*drug therapy/*etiology; Vitamin E/therapeutic use; Vitamins/therapeutic use; 80 and over; Artificial; Respiration; Artificial/*adverse effects; Randomized Controlled Trials; Double-Blind Studies; Acetylcysteine; Critically Ill Patients; Dietary Supplementation; Log-Rank Test; Mantel-Haenszel Test; Ventilator Weaning; Vitamin E; 80 and Over; Ascorbic Acid – Administration and Dosage
BACKGROUND: Many patients each year require prolonged mechanical ventilation. Inflammatory processes may prevent successful weaning, and evidence indicates that mechanical ventilation induces oxidative stress in the diaphragm, resulting in atrophy and contractile dysfunction of diaphragmatic myofibers. Antioxidant supplementation might mitigate the harmful effects of the oxidative stress induced by mechanical ventilation. OBJECTIVE: To test the clinical effectiveness of antioxidant supplementation in reducing the duration of mechanical ventilation. METHODS: A randomized, prospective, placebo-controlled double-blind design was used to test whether enterally administered antioxidant supplementation would decrease the duration of mechanical ventilation, all-cause mortality, and length of stay in the intensive care unit and hospital. Patients received vitamin C 1000 mg plus vitamin E 1000 IU, vitamin C 1000 mg plus vitamin E 1000 IU plus N-acetylcysteine 400 mg, or placebo solution as a bolus injection via their enteral feeding tube every 8 hours. RESULTS: Clinical and statistically significant differences in duration of mechanical ventilation were seen among the 3 groups (Mantel-Cox log rank statistic = 5.69, df = 1, P = .017). The 3 groups did not differ significantly in all-cause mortality during hospitalization or in the length of stay in the intensive care unit or hospital. CONCLUSIONS: Enteral administration of antioxidants is a simple, safe, inexpensive, and effective intervention that decreases the duration of mechanical ventilation in critically ill adults.
Howe Kimberly P; Clochesy John M; Goldstein Lawrence S; Owen Hugh
American journal of critical care : an official publication, American Association of Critical-Care Nurses
2015
2015-09
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<a href="http://doi.org/10.4037/ajcc2015335" target="_blank" rel="noreferrer noopener">10.4037/ajcc2015335</a>
The use of sensory electrical stimulation for pressure ulcer prevention.
Adult; Humans; Male; Middle Aged; Ohio; Aged; Double-Blind Method; Regional Blood Flow; *Electric Stimulation Therapy; Buttocks; Muscle Contraction; Paralysis/etiology/physiopathology/*therapy; Pressure Ulcer/etiology/physiopathology/*prevention & control; Sensory Thresholds; Spinal Cord Injuries/complications/physiopathology/*therapy; Treatment Failure; Tomography; Human; Funding Source; Repeated Measures; Outcome Assessment; Clinical Trials; Middle Age; X-Ray Computed; Muscle; Blood Gas Monitoring; Skeletal/blood supply/diagnostic imaging/*innervation; Transcutaneous; Double-Blind Studies; Interface Pressure; Spinal Cord Injuries; Time Series; Pressure Ulcer – Prevention and Control; Electric Stimulation – Methods; Electric Stimulation – Utilization; Skeletal – Radiography
Pressure ulcer prevention is critically important for many people with reduced mobility. The authors investigated whether sensory (sub-motor-threshold) electrical stimulation (ES) may provide a convenient preventive intervention. A double-blinded, repeated measures study design was used to test the hypothesis that repeated use of sensory surface ES improves tissue health status in individuals with motor paralysis. Six adult males with complete spinal cord injury (SCI) were randomly assigned to treatment or control groups. The treatment group received the ES intervention, whereas the control group received a control sham intervention. Repeated tissue health assessments included transcutaneous oxygen tension (T(c)PO(2)), interface pressure mapping, and gluteal computed tomography (CT) studies. An initial increase in T(c)PO(2) following use of subthreshold ES was observed but was not sustained at follow-up. No statistically significant changes before and after treatment were found in regional T(c)PO(2), gluteal muscle area or pressure distribution. Thus subthreshold ES does not appear to have any sustained effects on tissue health status indicative of reduced pressure ulcer risk for individuals with SCI. This implies that a contractile muscle response is critically important and further that subthreshold ES is unlikely to prevent pressure ulcers. Further studies are needed to find solutions for preventing pressure ulcers in high-risk populations.
Kim Jennifer; Ho Chester H; Wang Xiaofeng; Bogie Kath
Physiotherapy theory and practice
2010
2010-11
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<a href="http://doi.org/10.3109/09593981003587037" target="_blank" rel="noreferrer noopener">10.3109/09593981003587037</a>
A fixed-dose combination of adapalene 0.1%-BPO 2.5% allows an early and sustained improvement in quality of life and patient treatment satisfaction in severe acne.
Adult; Female; Humans; Male; Adolescent; Young Adult; Child; Severity of Illness Index; Quality of Life/*psychology; Double-Blind Method; *Patient Satisfaction; Drug Combinations; Acne Vulgaris/*drug therapy/*psychology; Adapalene; Benzoyl Peroxide/administration & dosage/*therapeutic use; Dermatologic Agents/administration & dosage/*therapeutic use; Naphthalenes/administration & dosage/*therapeutic use
INTRODUCTION: Acne has a significant negative impact on quality of life (QoL): lack of self-confidence, depressive symptoms and suicidal thoughts. The objective was to assess the impact of an initial and continued therapy in severe acne patients through patient-related outcomes (PRO). METHODS: In two sequential double-blind randomized studies, patients received either adapalene 0.1% and benzoyl peroxide 2.5% (A-BPO) or vehicle, associated with doxycycline 100 mg for 12 weeks. Patients having obtained at least a good improvement according to investigator global assessment were re-randomized for a 24-week therapy with
Brodell Robert T; Schlosser Bethanee J; Rafal Elyse; Toth Darryl; Tyring Stephen; Wertheimer Albert; Kerrouche Nabil; Bucher Delphine
The Journal of dermatological treatment
2012
2012-02
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<a href="http://doi.org/10.3109/09546634.2011.643221" target="_blank" rel="noreferrer noopener">10.3109/09546634.2011.643221</a>
Gemifloxacin versus amoxicillin/clavulanate in the treatment of acute exacerbations of chronic bronchitis. The 070 Clinical Study group.
*Fluoroquinolones; 80 and over; Acute-Phase Reaction; Adult; Aged; Amoxicillin/pharmacology/therapeutic use; Anti-Infective Agents/adverse effects/pharmacology/*therapeutic use; Bronchitis/*drug therapy; Chronic Disease; Clavulanic Acid/pharmacology/therapeutic use; Combination/pharmacology/*therapeutic use; Double-Blind Method; Drug Therapy; Female; Gemifloxacin; Haemophilus influenzae/drug effects; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Moraxella (Branhamella) catarrhalis/drug effects; Multicenter Studies as Topic; Naphthyridines/adverse effects/pharmacology/*therapeutic use; Streptococcus pneumoniae/drug effects; Treatment Outcome
Six hundred patients were evaluated in this randomized, double-blind, double-dummy, multicenter, parallel-group study comparing the efficacy and safety of gemifloxacin (320 mg once-daily for 5 days) and amoxicillin/clavulanate (500/125 mg three-times daily for 7 days) for the treatment of acute exacerbations of chronic bronchitis (AECB). Of note, more than 90% of study participants had stage 2 disease at study entry. The two drugs were found to be equally effective, with clinical success rates of 93.6% for gemifloxacin and 93.2% on amoxicillin/clavulanate (95% CI -3.9 to 4.6). Bacteriological success rates favored gemifloxacin (90.9% compared with 79.5% for amoxicillin/clavulanate; 95% CI -3.3 to 26.0); however, this difference was not statistically significant. Gemifloxacin and amoxicillin/clavulanate were both well tolerated. In summary, gemifloxacin was found to be well tolerated and effective for the treatment of AECB, suggesting it is well suited for empirical treatment of this common respiratory condition in the current clinical environment.
File T; Schlemmer B; Garau J; Lode H; Lynch S; Young C
Journal of chemotherapy (Florence, Italy)
2000
2000-08
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<a href="http://doi.org/10.1179/joc.2000.12.4.314" target="_blank" rel="noreferrer noopener">10.1179/joc.2000.12.4.314</a>
Topical brinzolamide (Azopt) versus placebo in the treatment of infantile nystagmus syndrome (INS).
Administration; Adult; Aged; Binocular/physiology; Carbonic Anhydrase Inhibitors/*therapeutic use; Clinical Trial; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscles; Nystagmus; Ophthalmic Solutions; Pathologic/*drug therapy/physiopathology; Prospective Studies; Sulfonamides/*therapeutic use; Thiazines/*therapeutic use; Topical; Treatment Medical; Vision; Visual Acuity/physiology
PURPOSE: To test the hypothesis that the topical carbonic anhydrase inhibitor brinzolamide (Azopt) has beneficial effects versus placebo on measures of nystagmus and visual acuity in adult subjects with infantile nystagmus syndrome (INS). DESIGN: Prospective, cross-over, double masked clinical trial. METHODS: SETTING: Single centre. STUDY POPULATION: Five subjects \textgreater/=18 years old with typical INS and best-binocular visual acuity in their primary position null zone ETDRS 55 letters to 85 letters (20/200 to 20/50) and had no previous treatment for nystagmus. INTERVENTION: In a randomised order, each subject received one drop of Azopt or placebo in both eyes three times a day separated by a washout period of at least a week followed by Azopt or placebo in both eyes three times a day; thus each subject got the drug and placebo, each acting as his or her own control. OUTCOME MEASURES: The nystagmus acuity function and INS waveforms obtained from eye movement recordings, binocular optotype visual acuity, using the ETDRS protocol analysed individually and as a group before and after Azopt and placebo. RESULTS: Versus placebo and baseline measures, topical Azopt significantly improved; INS waveform characteristics in the primary position null zone, group mean values of the nystagmus acuity function across gaze (p\textless0.01) and group mean ETDRS binocular letter visual acuity (p\textless0.05). There was a predictable decrease in intraocular pressure (IOP) without any systemic or ocular adverse events. CONCLUSIONS: Although a prospective large-scale clinical trial is needed to prove effectiveness, an eye-drop-based therapy for INS may emerge as a viable addition to optical, surgical, behavioural and systemic drug therapies for INS. TRIAL REGISTRATION NUMBER: NCT01312402.
Hertle Richard W; Yang Dongsheng; Adkinson Tonia; Reed Michael
The British journal of ophthalmology
2015
2015-04
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<a href="http://doi.org/10.1136/bjophthalmol-2014-305915" target="_blank" rel="noreferrer noopener">10.1136/bjophthalmol-2014-305915</a>
Intranasal lidocaine for the treatment of migraine headache: a randomized, controlled trial.
Administration; Adolescent; Adult; Anesthetics; Confidence Intervals; Double-Blind Method; Female; Hospitals; Humans; Intranasal; Lidocaine/*administration & dosage; Local; Male; Middle Aged; Migraine without Aura/diagnosis/*drug therapy; Ohio; Pain Measurement; Patient Satisfaction; Reference Values; Severity of Illness Index; Teaching; Treatment Outcome
OBJECTIVE: To evaluate the effect of intranasal lidocaine for immediate relief (5 minutes) of migraine headache pain. METHODS: A randomized, double-blind, placebo-controlled clinical trial at two university-affiliated community teaching hospitals enrolled patients 18-50 years old with migraine headache as defined by the International Headache Society. Patients who were pregnant, lactating, known to abuse alcohol or drugs, or allergic to one of the study drugs, those who used analgesics within two hours, or those with a first headache were excluded. Statistical significance was assessed by using chi-square or Fisher's exact test for categorical variables and Student's t-test for continuous variables. Patients rated their pain on a 10-centimeter visual analog scale (VAS) prior to drug administration and at 5, 10, 15, 20, and 30 minutes after the initial dose. Medication was either 1 mL of 4% lidocaine or normal saline (placebo) intranasally in split doses 2 minutes apart and intravenous prochlorperazine. Medications were packaged so physicians and patients were unaware of the contents. Successful pain relief was achieved if there was a 50% reduction in pain score or a score below 2.5 cm on the VAS. RESULTS: Twenty-seven patients received lidocaine and 22 placebo. No significant difference was observed between groups in initial pain scores, 8.4 (95% CI = 7.8 to 9.0) lidocaine and 8.6 (95% CI = 8.0 to 9.2) placebo (p = 0.75). Two of 27 patients (7.4%, 95% CI = 0.8, 24.3) in the lidocaine group and three of 22 patients (13.6%, 95% CI = 2.8 to 34.9) in the placebo group had immediate successful pain relief (p = 0.47), with average pain scores of 6.9 (95% CI = 5.9 to 7.8) and 7.0 (95% CI = 5.8 to 8.2), respectively. No difference in pain relief was detected at subsequent measurements. CONCLUSION: There was no evidence that intranasal lidocaine provided rapid relief for migraine headache pain in the emergency department setting.
Blanda M; Rench T; Gerson L W; Weigand J V
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine
2001
2001-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1111/j.1553-2712.2001.tb02111.x" target="_blank" rel="noreferrer noopener">10.1111/j.1553-2712.2001.tb02111.x</a>
Dialysis leg cramps. Efficacy of quinine versus vitamin E.
Adult; Aged; Double-Blind Method; Female; Humans; Leg; Male; Middle Aged; Muscle Cramp/*drug therapy/etiology; Quinine/*therapeutic use; Renal Dialysis/*adverse effects; Vitamin E/*therapeutic use
A controlled randomized double-blind study was done to determine the frequency and severity of leg cramps in 40 patients on dialysis with a history of leg cramps. All patients entered a 2 month placebo washout and were randomized into a 2 month double-dummy phase of quinine 325 mg at bedtime versus vitamin E 400 IU at bedtime. Of the 29 patients completing the study, 16 received quinine and 13 vitamin E. During placebo washout, the vitamin E group had a mean of 10.4 leg cramps per month, and the quinine group had a mean of 10.9. The vitamin E and quinine groups had a 1 month reduction in leg cramps to 3.3 and 3.6, respectively (p \textless 0.0005 for both groups combined); this was sustained at 2 months. A severity of pain index showed a statistically significant decrease for both groups. The 95% confidence interval for the difference between the number of leg cramps after vitamin E versus quinine treatment (95% confidence interval, -3.8, +3.2) suggests similar efficacy. Quinine and vitamin E were effective treatments for leg cramps in these patients. Considering the potential toxicity of quinine, vitamin E is recommended as the initial treatment of choice for patients on dialysis with leg cramps.
Roca A O; Jarjoura D; Blend D; Cugino A; Rutecki G W; Nuchikat P S; Whittier F C
ASAIO journal (American Society for Artificial Internal Organs : 1992)
1992
1992-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1097/00002480-199207000-00081" target="_blank" rel="noreferrer noopener">10.1097/00002480-199207000-00081</a>
FOCUS 1: a randomized, double-blinded, multicentre, Phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia.
80 and over; 80 and Over; Aged; Bacteria; Bacteria/isolation & purification; Bacterial – Drug Therapy; Bacterial/*drug therapy; Ceftriaxone – Administration and Dosage; Ceftriaxone – Adverse Effects; Ceftriaxone/administration & dosage/adverse effects; Cephalosporins – Administration and Dosage; Cephalosporins – Adverse Effects; Cephalosporins/*administration & dosage/*adverse effects; Community-Acquired Infections – Drug Therapy; Community-Acquired Infections/*drug therapy; Double-Blind Method; Double-Blind Studies; Female; Human; Humans; Infusions; Intravenous; Male; Middle Age; Middle Aged; Pneumonia; Randomized Controlled Trials; Treatment Outcome; Treatment Outcomes
OBJECTIVES: Ceftaroline, the active form of the prodrug ceftaroline fosamil, is a novel cephalosporin with bactericidal activity against important pathogens associated with community-acquired pneumonia (CAP), including Streptococcus pneumoniae and common Gram-negative pathogens. FOCUS 1 is a randomized, double-blinded, Phase III study that was conducted to evaluate the efficacy and safety of ceftaroline fosamil in treating patients with CAP. The primary objective was to determine non-inferiority [lower limit of 95% confidence interval (CI) \textgreater/= -10%] in clinical cure rates achieved with ceftaroline fosamil compared with those achieved with ceftriaxone in the clinically evaluable (CE) and modified intent-to-treat efficacy (MITTE) populations. METHODS: Patients hospitalized in a non-intensive care unit setting with CAP of Pneumonia Outcomes Research Team (PORT) risk class III or IV requiring intravenous (iv) therapy were randomized (1:1) to receive 600 mg of ceftaroline fosamil iv every 12 h or 1 g of ceftriaxone iv every 24 h. Patients also received two 500 mg doses of oral clarithromycin every 12 h administered on day 1. Clinical cure, microbiological response, adverse events (AEs) and laboratory tests were assessed. FOCUS 1 registration number NCT00621504 (http://clinicaltrials.gov/ct2/show/NCT00621504). RESULTS: Of 613 enrolled patients, 298 received ceftaroline fosamil and 308 received ceftriaxone. Baseline characteristics between treatment groups were comparable. Clinical cure rates were as follows: CE population, 86.6% (194/224) for ceftaroline fosamil and 78.2% (183/234) for ceftriaxone [difference (95% CI), 8.4% (1.4, 15.4)]; and MITTE population, 83.8% (244/291) for ceftaroline fosamil and 77.7% (233/300) for ceftriaxone [difference (95% CI), 6.2% (-0.2, 12.6)]. Clinical cure rates for CAP caused by S. pneumoniae in the microbiological MITTE population were 88.9% (24/27) and 66.7% (20/30) for ceftaroline fosamil and ceftriaxone, respectively. Both agents were well tolerated, with similar rates of AEs, serious AEs, deaths and discontinuations because of an AE. The most common AEs for ceftaroline fosamil-treated patients were diarrhoea, headache, insomnia and nausea, and the most common AEs for ceftriaxone-treated patients were hypokalaemia, hypertension, nausea and diarrhoea. CONCLUSIONS: Ceftaroline fosamil demonstrated high clinical cure and microbiological response rates in hospitalized patients with CAP of PORT risk class III or IV. Ceftaroline fosamil was well tolerated, with a safety profile similar to that of ceftriaxone and consistent with the cephalosporin class. In this study, ceftaroline fosamil was an effective and well-tolerated treatment option for CAP.
File Thomas M Jr; Low Donald E; Eckburg Paul B; Talbot George H; Friedland H David; Lee Jon; Llorens Lily; Critchley Ian A; Thye Dirk A
The Journal of antimicrobial chemotherapy
2011
2011-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1093/jac/dkr096" target="_blank" rel="noreferrer noopener">10.1093/jac/dkr096</a>
Gemifloxacin once daily for 5 days versus 7 days for the treatment of community-acquired pneumonia: a randomized, multicentre, double-blind study.
80 and over; Adolescent; Adult; Aged; Anti-Bacterial Agents/*administration & dosage/adverse effects/therapeutic use; Bacterial/*drug therapy/microbiology; Community-Acquired Infections/*drug therapy/microbiology; Double-Blind Method; Drug Administration Schedule; Female; Fluoroquinolones/*administration & dosage/adverse effects/therapeutic use; Gemifloxacin; Humans; Male; Middle Aged; Naphthyridines/*administration & dosage/adverse effects/therapeutic use; Pneumococcal/drug therapy/microbiology; Pneumonia; Streptococcus pneumoniae/isolation & purification; Treatment Outcome
OBJECTIVES: Short-course therapy has been advocated for the treatment of community-acquired pneumonia (CAP). We compared the efficacy and safety of 5 and 7 day courses of gemifloxacin for outpatient treatment of mild-moderate CAP. PATIENTS AND METHODS: In a multicentre, double-blind, parallel group study, patients were randomized to receive 320 mg of oral gemifloxacin once daily for 5 or 7 days. Over 95% of all patients in each cohort had a Fine score of
File Thomas M Jr; Mandell Lionel A; Tillotson Glenn; Kostov Kosta; Georgiev Ognian
The Journal of antimicrobial chemotherapy
2007
2007-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1093/jac/dkm119" target="_blank" rel="noreferrer noopener">10.1093/jac/dkm119</a>
Integrated analysis of FOCUS 1 and FOCUS 2: randomized, doubled-blinded, multicenter phase 3 trials of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in patients with community-acquired pneumonia.
80 and over; Administration; Adult; Aged; Anti-Bacterial Agents/*administration & dosage/*adverse effects; Bacterial/*drug therapy; Ceftriaxone/*administration & dosage/*adverse effects; Cephalosporins/*administration & dosage/*adverse effects; Community-Acquired Infections/drug therapy; Double-Blind Method; Female; Humans; Infusions; Intravenous; Male; Middle Aged; Oral; Pneumonia; Treatment Outcome
BACKGROUND: Ceftaroline, the active form of ceftaroline fosamil, is a broad-spectrum cephalosporin with bactericidal activity against pathogens causing community-acquired pneumonia (CAP), including Streptococcus pneumoniae. Ceftaroline was evaluated for the treatment of CAP in 2 randomized, double-blind, multicenter trials: Ceftaroline Community Acquired Pneumonia Trial versus Ceftriaxone in Hospitalized Patients (FOCUS) 1 and FOCUS 2. METHODS: Patients hospitalized (but not admitted to an intensive care unit) with Pneumonia Outcomes Research Team risk class III or IV CAP requiring intravenous therapy were randomized to ceftaroline 600 mg every 12 h or ceftriaxone 1 g every 24 h for 5-7 days. Patients in FOCUS 1 received 2 doses of oral clarithromycin 500 mg every 12 h on day 1. RESULTS: In the individual trials, clinical cure rates in the clinically evaluable (CE) population for ceftaroline versus ceftriaxone were as follows: FOCUS 1, 86.6% vs 78.2% (difference, 8.4%; 95% confidence interval [CI], 1.4%-15.4%); FOCUS 2, 82.1% vs 77.2% (difference, 4.9%; 95% CI, -2.5% to 12.5%). In the integrated analysis, 614 patients received ceftaroline and 614 received ceftriaxone. Of the CE patients treated with ceftaroline, 84.3% achieved clinical cure, compared with 77.7% of ceftriaxone-treated patients (difference, 6.7%; 95% CI, 1.6%-11.8%). Clinical cure rates in the modified intent-to-treat efficacy population were 82.6% versus 76.6% for ceftaroline and ceftriaxone (difference, 6.0%; 95% CI, 1.4%-10.7%). Ceftaroline and ceftriaxone were well tolerated; rates of adverse events, serious adverse events, deaths, and premature discontinuations caused by an adverse event were similar in both treatment arms. CONCLUSIONS: Ceftaroline was noninferior to ceftriaxone in the individual trials. In this integrated analysis, clinical cure rates for the ceftaroline group were numerically higher than those for the ceftriaxone group. Ceftaroline was well tolerated, with a safety profile similar to that of ceftriaxone.
File Thomas M Jr; Low Donald E; Eckburg Paul B; Talbot George H; Friedland H David; Lee Jon; Llorens Lily; Critchley Ian; Thye Dirk
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
2010
2010-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1086/657313" target="_blank" rel="noreferrer noopener">10.1086/657313</a>
The bronchodilator effect of intravenous glucagon in asthma exacerbation: a randomized, controlled trial.
Adult; Asthma/complications/*drug therapy; Bronchodilator Agents/*administration & dosage; Double-Blind Method; Female; Glucagon/*administration & dosage; Humans; Injections; Intravenous; Male
STUDY OBJECTIVE: Glucagon is a rapid-acting smooth muscle relaxant with a short half-life. Previous studies suggested glucagon may have bronchodilator effects. We sought to determine whether intravenous glucagon produces clinically important immediate bronchodilation in emergency department patients with asthma exacerbation. METHODS: We conducted a randomized, double-blind, placebo-controlled study at 2 university-affiliated community teaching hospital EDs (annual census 90,000). ED patients 18 to 50 years old with asthma exacerbation and peak expiratory flow rate (PEFR) less than 350 L/min were eligible. Exclusion criteria were need for intubation, chronic obstructive pulmonary disease, diabetes mellitus, insulinoma, pheochromocytoma, pregnancy, lactation, or current oral steroid treatment. Patients were randomly assigned to receive glucagon 0.03 mg/kg or an equivalent volume of saline solution intravenously. At 10 minutes, PEFR was measured and all patients began standardized albuterol therapy. Successful bronchodilation was a PEFR increase of 60 L/min at 10 minutes. RESULTS: Success occurred in 2 (9.5%) of 21 glucagon-treated patients and 3 (12%) of 25 placebo-treated patients (95% confidence interval [CI] for difference of -2.5% [-20.4% to 15. 4%]). Mean PEFR improvement for glucagon was 2 L/min versus 9 L/min for placebo (95% CI for difference of -7 L/min [-36 L/min to 23 L/min]). CONCLUSION: Glucagon alone provided no clinically important immediate bronchodilation in ED patients with asthma exacerbation.
Wilber S T; Wilson J E; Blanda M; Gerson L W; Meerbaum S O; Janas G
Annals of emergency medicine
2000
2000-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1067/mem.2000.110823" target="_blank" rel="noreferrer noopener">10.1067/mem.2000.110823</a>
Outcome of treatment of respiratory tract infections due to Streptococcus pneumoniae, including drug-resistant strains, with pharmacokinetically enhanced amoxycillin/clavulanate.
*Treatment Outcome; 80 and over; Adolescent; Adult; Aged; Amoxicillin-Potassium Clavulanate Combination/administration & dosage/*pharmacokinetics/pharmacology/*therapeutic use; Amoxicillin/adverse effects/therapeutic use; Bacterial; Bacterial/drug therapy/immunology; Bronchitis/drug therapy/microbiology; Combination/adverse effects/*therapeutic use; Double-Blind Method; Drug Administration Schedule; Drug Resistance; Drug Therapy; Female; Follow-Up Studies; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Multicenter Studies as Topic; Pneumonia; Respiratory Tract Infections/*drug therapy/metabolism/microbiology; Streptococcal Infections/*drug therapy/metabolism/microbiology; Streptococcus pneumoniae/*drug effects
The efficacy of a new pharmacokinetically enhanced formulation of amoxycillin/clavulanate (AMX/CA) 2000/125 mg, twice daily, designed to provide adequate levels of amoxycillin over the 12-h dosing interval to eradicate penicillin-resistant Streptococcus pneumoniae (PRSP) with amoxycillin (+/-clavulanic acid) MICs of
File Thomas M Jr; Jacobs Michael R; Poole Michael D; Wynne Brian
International journal of antimicrobial agents
2002
2002-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0924-8579(02)00130-9" target="_blank" rel="noreferrer noopener">10.1016/s0924-8579(02)00130-9</a>
Macrolide therapy for community-acquired pneumonia due to atypical pathogens: outcome assessment at an early time point.
80 and over; Adult; Aged; Anti-Bacterial Agents/adverse effects/*therapeutic use; Atypical pathogen; Bacterial/*drug therapy; Ceftaroline fosamil; Ceftriaxone/adverse effects/*therapeutic use; Cephalosporins/adverse effects/*therapeutic use; Chlamydial Pneumonia; Chlamydophila pneumoniae; Clinical Trials; Combination/adverse effects/methods; Community-Acquired Infections/*drug therapy; Community-acquired pneumonia; Double-Blind Method; Drug Therapy; Female; Humans; Legionella pneumophila; Macrolide; Macrolides/adverse effects/*therapeutic use; Male; Middle Aged; Mycoplasma; Mycoplasma pneumoniae; Phase III as Topic; Pneumonia; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome
BACKGROUND: Therapy directed against atypical pathogens in patients with community-acquired pneumonia (CAP) is often recommended. This post-hoc analysis evaluated the effect of addition of a macrolide to ceftaroline fosamil or ceftriaxone treatment in atypical CAP. METHODS: Two phase 3, double-blind, comparative safety and efficacy studies of ceftaroline fosamil vs. ceftriaxone, FOCUS 1 and FOCUS 2, enrolled adults with CAP. Only FOCUS 1 included 24-h adjunctive clarithromycin therapy for all patients on day 1. Day 4 and test-of-cure (TOC) outcomes were compared for adjunctive vs. no adjunctive therapy. RESULTS: Of 1240 enrolled patients, 130 patients with CAP due to atypical pathogens alone were included (FOCUS 1, n = 64; FOCUS 2, n = 66). Among patients infected with Mycoplasma pneumoniae and/or Chlamydophila pneumoniae alone, a higher clinical response rate was observed with clarithromycin plus ceftaroline fosamil or ceftriaxone compared with treatment without additional clarithromycin at day 4 [38/49 (77.6%; FOCUS 1) vs. 24/43 (55.8%; FOCUS 2)], but not at the TOC assessment [42/49 (85.7%; FOCUS 1) vs. 41/43 (95.3%; FOCUS 2)]. In patients infected with Legionella pneumophila alone, a higher clinical response rate with adjunctive clarithromycin therapy was observed at the TOC assessment alone [12/12 (100%; FOCUS 1) vs. 14/19 (73.7%; FOCUS 2)]. The unadjusted odds ratio of a favourable clinical response at day 4 with adjunctive clarithromycin vs. no adjunctive clarithromycin was 2.4 (95% confidence interval 1.1-5.1; P = 0.0299) for all pathogens combined. CONCLUSIONS: These results suggest that empirical antibiotic therapy against atypical pathogens may improve early clinical response rate. This hypothesis is best evaluated in a prospective trial.
File Thomas M Jr; Eckburg Paul B; Talbot George H; Llorens Lily; Friedland H David
International journal of antimicrobial agents
2017
2017-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.ijantimicag.2017.01.043" target="_blank" rel="noreferrer noopener">10.1016/j.ijantimicag.2017.01.043</a>
Does preoperative rofecoxib (Vioxx) decrease postoperative pain with laparoscopic cholecystectomy?
Adult; Anti-Inflammatory Agents; Cholecystectomy; Double-Blind Method; Female; Humans; Lactones/*administration & dosage; Laparoscopic/*adverse effects; Male; Middle Aged; Non-Steroidal/*administration & dosage; Pain; Postoperative/drug therapy/etiology/*prevention & control; Preoperative Care; Prospective Studies; Sulfones; Treatment Outcome
BACKGROUND: A prospective, randomized, double-blinded clinical trial was designed to study the effects of preemptive rofecoxib (Vioxx) analgesia in patients undergoing elective laparoscopic cholecystectomy. METHODS: One hundred-twenty patients were enrolled in the study over a 21-month period, and 116 completed the study. One half of the patients received 50 mg rofecoxib preoperatively and the other half, placebo. Both groups were demographically similar. Medical information, patient and nursing assessments, and surgical data were evaluated. RESULTS: A significant reduction in requirements for postoperative narcotic analgesic dosing was noted in the rofecoxib group. In addition, patients receiving rofecoxib reported significantly less nausea and improvement in their activity level when compared with the control group. No complications were encountered with the preoperative use of rofecoxib. CONCLUSIONS: We conclude that in patients undergoing laparoscopic cholecystectomy, preoperative administration of rofecoxib in selected patients may facilitate postoperative recovery and decrease postoperative narcotic requirements.
Horattas Mark C; Evans Steve; Sloan-Stakleff Kimberly D; Lee Christopher; Snoke Joseph W
American journal of surgery
2004
2004-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.amjsurg.2004.06.007" target="_blank" rel="noreferrer noopener">10.1016/j.amjsurg.2004.06.007</a>
Adverse reactions to aspartame: double-blind challenge in patients from a vulnerable population.
Adult; Aspartame/*adverse effects/*therapeutic use; Cross-Sectional Studies; Depressive Disorder/diagnosis/*drug therapy/psychology; Double-Blind Method; Eye Diseases/etiology/physiopathology; Female; Headache/etiology; Humans; Male; Middle Aged; Placebos; Psychiatric Status Rating Scales; Vision Disorders/etiology/physiopathology
This study was designed to ascertain whether individuals with mood disorders are particularly vulnerable to adverse effects of aspartame. Although the protocol required the recruitment of 40 patients with unipolar depression and a similar number of individuals without a psychiatric history, the project was halted by the Institutional Review Board after a total of 13 individuals had completed the study because of the severity of reactions within the group of patients with a history of depression. In a crossover design, subjects received aspartame 30 mg/kg/day or placebo for 7 days. Despite the small n, there was a significant difference between aspartame and placebo in number and severity of symptoms for patients with a history of depression, whereas for individuals without such a history there was not. We conclude that individuals with mood disorders are particularly sensitive to this artificial sweetener and its use in this population should be discouraged.
Walton R G; Hudak R; Green-Waite R J
Biological psychiatry
1993
1993-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0006-3223(93)90251-8" target="_blank" rel="noreferrer noopener">10.1016/0006-3223(93)90251-8</a>