Cranberry versus placebo in the prevention of urinary infections in multiple sclerosis: a multicenter, randomized, placebo-controlled, double-blind trial

2014 ◽  
Vol 20 (9) ◽  
pp. 1252-1259 ◽  
Author(s):  
Philippe Gallien ◽  
Gérard Amarenco ◽  
Nicolas Benoit ◽  
Véronique Bonniaud ◽  
Cécile Donzé ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Double Blind Study ◽  
Sequential Method ◽  
Double Blind ◽  
Urinary Disorders ◽  
Symptomatic Urinary Tract Infection ◽  
Urinary Infections ◽  
Secondary Endpoints ◽  
Intent To Treat ◽  
Sequential Analyses

Objective: Our aim was to assess the usefulness of cranberry extract in multiple sclerosis (MS) patients suffering from urinary disorders. Methods: In total, 171 adult MS outpatients with urinary disorders presenting at eight centers were randomized (stratification according to center and use of clean intermittent self-catheterization) to cranberry versus placebo in a 1-year, prospective, double-blind study that was analyzed using a sequential method on an intent-to-treat basis. An independent monitoring board analyzed the results of the analyses each time 40 patients were assessed on the main endpoint. Cranberry extract (36 mg proanthocyanidins per day) or a matching placebo was taken by participants twice daily for 1 year. The primary endpoint was the time to first symptomatic urinary tract infection (UTI), subject to validation by a validation committee. Results: The second sequential analyses allowed us to accept the null hypothesis (no difference between cranberry and placebo). There was no difference in time to first symptomatic UTI distribution across 1 year, with an estimated hazard ratio of 0.99, 95% CI [0.61, 1.60] ( p = 0.97). Secondary endpoints and tolerance did not differ between groups. Conclusion: Taking cranberry extract versus placebo twice a day did not prevent UTI occurrence in MS patients with urinary disorders. Trial Registration NCT00280592.

scholarly journals Rezafungin versus Caspofungin in a Phase 2, Randomized, Double-Blind Study for the Treatment of Candidemia and Invasive Candidiasis- The STRIVE Trial

2020 ◽  
Author(s):  
George R Thompson ◽  
Alex Soriano ◽  
Athanasios Skoutelis ◽  
Jose A Vazquez ◽  
Patrick M Honore ◽  
...  
Keyword(s):  
Invasive Candidiasis ◽  
Double Blind Study ◽  
Phase 2 ◽  
Double Blind ◽  
Once Daily ◽  
Secondary Endpoints ◽  
Intent To Treat ◽  
Cure Rates ◽  
Treat Population

Abstract Background Rezafungin (RZF) is a novel echinocandin exhibiting distinctive pharmacokinetics/pharmacodynamics. STRIVE was a phase 2, double-blind, randomized trial designed to compare the safety and efficacy of RZF once weekly (QWk) to caspofungin (CAS) once daily for treatment of candidemia and/or invasive candidiasis (IC). Methods Adults with systemic signs and mycological confirmation of candidemia and/or IC were randomized to RZF 400 mg QWk (400 mg), RZF 400 mg on week 1 then 200 mg QWk (400/200 mg), or CAS 70 mg as a loading dose followed by 50 mg daily for ≤ 4 weeks. Efficacy assessments included overall cure (resolution of signs of candidemia/IC + mycological eradication) at day 14 (primary endpoint), investigator-assessed clinical response at day 14, and 30-day all-cause mortality (ACM) (secondary endpoints), and time to negative blood culture. Safety was evaluated by adverse events and ACM through follow-up. Results Of 207 patients enrolled, 183 were in the microbiological intent-to-treat population (~21% IC). Overall cure rates were 60.5% (46/76) for RZF 400 mg, 76.1% (35/46) for RZF 400/200 mg, and 67.2% (41/61) for CAS; investigator-assessed clinical cure rates were 69.7% (53/76), 80.4% (37/46), and 70.5% (43/61), respectively. 30-day ACM was 15.8% for RZF 400 mg, 4.4% for RZF 400/200 mg, and 13.1% for CAS. Candidemia was cleared in 19.5 and 22.8 hours in RZF and CAS patients, respectively. No concerning safety trends were observed; ACM through follow-up was 15.2% (21/138) for RZF and 18.8% (13/69) for CAS. Conclusions RZF was safe and efficacious in the treatment of candidemia and/or IC.

A randomized, controlled trial of fingolimod (FTY720) in Japanese patients with multiple sclerosis

2012 ◽  
Vol 18 (9) ◽  
pp. 1269-1277 ◽  
Author(s):  
T Saida ◽  
S Kikuchi ◽  
Y Itoyama ◽  
Q Hao ◽  
T Kurosawa ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Phase Ii ◽  
Clinical Efficacy ◽  
Controlled Trial ◽  
Japanese Patients ◽  
Double Blind ◽  
Parallel Group ◽  
Safety Outcomes ◽  
Secondary Endpoints ◽  
Caucasian Patients

Background: Fingolimod (FTY720) has previously shown clinical efficacy in phase II/III studies of predominantly Caucasian populations with multiple sclerosis (MS). Objectives: To report six-month efficacy and safety outcomes in Japanese patients with relapsing MS treated with fingolimod. Methods: In this double-blind, parallel-group, phase II study, 171 Japanese patients with relapsing MS were randomized to receive once-daily fingolimod 0.5 mg or 1.25 mg, or matching placebo for six months. The primary and secondary endpoints were the percentages of patients free from gadolinium (Gd)-enhanced lesions at months 3 and 6, and relapses over six months, respectively; safety outcomes were also assessed. Results: 147 patients completed the study. Higher proportions of patients were free from Gd-enhanced lesions at months 3 and 6 with fingolimod (0.5 mg: 70%, p = 0.004; 1.25 mg: 86%, p < 0.001) than with placebo (40%). Odds ratios for the proportions of relapse-free patients over six months favoured fingolimod versus placebo but were not significant. Adverse events related to fingolimod included transient bradycardia and atrioventricular block at treatment initiation, and elevated liver enzyme levels. Conclusions: This study demonstrated the clinical efficacy of fingolimod for the first time in Japanese patients with MS, consistent with the established effects of fingolimod in Caucasian patients.

HAGIL (Hamburg Vigil Study): a randomized placebo-controlled double-blind study with modafinil for treatment of fatigue in patients with multiple sclerosis

2011 ◽  
Vol 17 (8) ◽  
pp. 1002-1009 ◽  
Author(s):  
F Möller ◽  
J Poettgen ◽  
F Broemel ◽  
A Neuhaus ◽  
M Daumer ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Safety Concern ◽  
Dropout Rate ◽  
Secondary Outcome ◽  
Controlled Study ◽  
Double Blind Study ◽  
Double Blind ◽  
Neuropsychological Measures ◽  
Intention To Treat

Objective: To reassess the effect of modafinil, a wakefulness-promoting artificial psychostimulant, on fatigue and neuropsychological measures in patients with multiple sclerosis. Methods: Multiple sclerosis (MS) patients with a baseline score of ≥4 on the Fatigue Severity Scale (FSS) and an Expanded Disability Status Scale score <7 were eligible for the 8-week randomized, double-blind, placebo-controlled study. Modafinil was dosed up to 200 mg/day within 1 week. Assessments were performed at baseline and after 4 and 8 weeks. The primary outcome parameter was the mean change of the FSS mean score. Secondary outcome variables were other questionnaires covering fatigue, daytime sleepiness and sleep quality. Cognitive impairment was assessed by the oral version of the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT). Results: The study included 121 MS patients. Dropout rate was 9%. Both treatment groups showed improvements through time. While mean FSS at 8 weeks showed a trend difference between groups in the intention-to-treat analysis, the primary endpoint was not met. Assessment of cognitive impairment by SDMT and PASAT showed contradictory results. All other secondary endpoints were not met. There was no major safety concern. Conclusions: In general, the study does not support modafinil as an effective treatment for MS fatigue. However, the study shows the need for new study designs and endpoints in MS fatigue studies.

A double-blind, cross-over trial of intravenous immunoglobulin G in multiple sclerosis: Preliminary results

1997 ◽  
Vol 3 (2) ◽  
pp. 145-148 ◽  
Author(s):  
P. Soelberg Sørensen ◽  
B. Wanscher ◽  
K. Schreiber ◽  
M. Blinkenberg ◽  
C.V. Jensen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Intravenous Immunoglobulin ◽  
Immunoglobulin G ◽  
Progressive Multiple Sclerosis ◽  
Ivig Treatment ◽  
Double Blind Study ◽  
Intravenous Methylprednisolone ◽  
Double Blind ◽  
Relapsing Remitting ◽  
Intravenous Immunoglobulin G

We enrolled 25 patients with relapsing-remitting or relapsing progressive multiple sclerosis (MS) in a randomized placebo-controlled double-blind study of intravenous immunoglobulin G (IVIG). IVIG Iglkg daily for 2 days was administered every 4 weeks for 24 weeks. Seventeen patients completed the whole trial, whereas eight patients discontinued the trial; four during IVIG treatment and four on placebo. Of the 17 patients who completed the trial, II had no exacerbations during IVIG treatment compared with only six on placebo (P=0.05). The total number of exacerbations in the IVIG period was I / and in the placebo period 15 (NS), and the number of severe exacerbations requiring treatment with intravenous methylprednisolone was four during treatment with IVIG and six on placebo (NS). The results suggest that IVIG treatment may be of beneft for prevention of exacerbations in patients with relapsing MS.

scholarly journals A Phase 3, double-blind, placebo-controlled efficacy and safety study of ADS-5102 (Amantadine) extended-release capsules in people with multiple sclerosis and walking impairment

2021 ◽  
pp. 135245852110353
Author(s):  
Jeffrey A Cohen ◽  
Michelle H Cameron ◽  
Myla D Goldman ◽  
Andrew D Goodman ◽  
Aaron E Miller ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Extended Release ◽  
Walking Speed ◽  
Testing Procedure ◽  
Double Blind Study ◽  
Phase 3 ◽  
Timed Up And Go ◽  
Double Blind ◽  
Meaningful Improvement

Background: ADS-5102, a delayed-release, extended-release (DR/ER) amantadine, improved walking speed in MS in a Phase 2 trial. Objective: The aim of this study was to present primary results of a Phase 3, double-blind, ADS-5102 trial (INROADS) for walking speed. Methods: Adult participants with MS and walking impairment, not currently using amantadine or dalfampridine, underwent 4-week placebo run-in before randomization 1:1:1 to placebo, 137 or 274 mg/day ADS-5102 for 12 weeks. Primary outcome was the proportion of responders (20% increase in Timed 25-Foot Walk (T25FW) speed) for 274 mg ADS-5102 versus placebo at end of double-blind (Study Week 16). Additional measures included Timed Up and Go (TUG), 2-Minute Walk Test (2MWT), and 12-item Multiple Sclerosis Walking Scale (MSWS-12). Results: In total, 558 participants were randomized and received double-blind treatment. Significantly more participants responded with 274 mg ADS-5102 (21.1%) versus placebo (11.3%). Mean T25FW speed also significantly improved (0.19 ft/s) versus placebo (0.07 ft/s). Other measures were not significant using prespecified hierarchical testing procedure. Adverse events led to discontinuation for 3.8% (placebo), 6.4% (137 mg ADS-5102), and 20.5% (274 mg ADS-5102). Conclusion: INROADS met its primary endpoint, showing a significantly greater proportion of participants with meaningful improvement in walking speed for 274 mg ADS-5102 versus placebo. Numeric dose response was seen for some secondary efficacy outcomes and adverse events.

scholarly journals 110. A Phase 3, Multicenter, Double-blind, Randomized Clinical Trial to Evaluate the Efficacy and Safety of Ceftolozane/Tazobactam Plus Metronidazole Versus Meropenem in Chinese Participants With Complicated Intra-abdominal Infections

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S67-S68
Author(s):  
Yihong Sun ◽  
Jia Fan ◽  
Gang Chen ◽  
Xiaofei Chen ◽  
Xiaoling Du ◽  
...  
Keyword(s):  
Clinical Cure ◽  
Additional Treatment ◽  
Double Blind Study ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
Study Drug Administration ◽  
Treatment Groups ◽  
Secondary Endpoints ◽  
Abdominal Infections

Abstract Background In China, the prevalence of infections due to multidrug-resistant gram-negative bacteria is high and additional treatment options for complicated intra-abdominal infections (cIAI) are needed. This study compared the efficacy and safety of ceftolozane/tazobactam (C/T) + metronidazole (MTZ) versus meropenem (MEM) + placebo (pbo) for the treatment of cIAI in adult Chinese participants. Methods This was a phase 3, double-blind study conducted at 21 centers in China (NCT03830333). Participants aged 18-75 years with cIAI requiring surgical intervention within 24 hours of study drug administration were stratified by site of infection and randomized 1:1 to receive 1.5 g C/T (1 g ceftolozane and 0.5 g tazobactam) + 0.5 g MTZ administered intravenously (IV) every 8 hours (q8h) or 1 g MEM + pbo administered IV q8h for 4-14 days. The primary endpoint was clinical cure at test of cure (TOC) in the clinically evaluable (CE) population. Secondary endpoints included rates of clinical cure, per-participant microbiologic response, per-pathogen microbiologic response, and adverse events (AE). Non-inferiority for clinical cure at TOC in the CE population was confirmed if the lower bound of the 2-sided 95% CI for the between-treatment difference in the clinical cure rate was larger than −12.5%. Results A total of 134 participants were randomized to each treatment group. Demographics and baseline characteristics were generally well balanced between treatment groups (Table 1). The median (range) age in the ITT population was 50 (18-75) years and 61% were men. The most frequent sites of infection were the appendix (C/T + MTZ, 50.0%; MEM + pbo, 49.3%) and gallbladder (C/T + MTZ, 27.6%; MEM + pbo, 29.1%). Overall, the most frequently isolated pathogens were Escherichia coli (61.4%) and Klebsiella pneumoniae (17.3%); few anaerobes were isolated (Table 1). C/T + MTZ was non-inferior to MEM + pbo for clinical cure in the CE population (C/T + MTZ, 95.2%; MEM + pbo, 93.1%; difference, 2.1% [95% CI, −4.7% to 8.8%]). Results for key secondary endpoints were comparable between treatment groups (Table 2). Rates of AEs were generally similar between treatment groups (Table 3). Conclusion C/T + MTZ was non-inferior to MEM + pbo in the treatment of adult Chinese participants with cIAI and demonstrated a favorable safety profile. Disclosures Xiaofei Chen, n/a, MSD, China (Employee) Xiaoling Du, n/a, MSD, China (Employee) Ye Wang, n/a, MSD, China (Employee) Hui Wang, n/a, MSD, China (Employee) Fang Sun, n/a, MSD, China (Employee) Matthew G. Johnson, MD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee) Mekki Bensaci, PhD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee) Jennifer A. Huntington, PharmD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee) Christopher Bruno, MD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee)

scholarly journals Double blind study of intrathecal beta-interferon in multiple sclerosis: clinical and laboratory results.

1990 ◽  
Vol 53 (7) ◽  
pp. 554-557 ◽  
Author(s):  
C Milanese ◽  
A Salmaggi ◽  
L La Mantia ◽  
A Campi ◽  
M Eoli ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Blind Study ◽  
Double Blind Study ◽  
Double Blind ◽  
Beta Interferon ◽  
Laboratory Results

scholarly journals Natalizumab versus fingolimod for patients with active relapsing-remitting multiple sclerosis: results from REVEAL, a prospective, randomised head-to-head study

BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e038861
Author(s):  
Helmut Butzkueven ◽  
Stephanie Licata ◽  
Douglas Jeffery ◽  
Douglas L Arnold ◽  
Massimo Filippi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cumulative Probability ◽  
T2 Lesions ◽  
Parallel Group ◽  
Relapsing Remitting ◽  
Patients At Risk ◽  
Secondary Endpoints ◽  
Remitting Multiple Sclerosis ◽  
Intent To Treat ◽  
Relapsing Remitting Multiple Sclerosis

ObjectiveTo directly compare the efficacy of natalizumab and fingolimod in patients with active relapsing-remitting multiple sclerosis.MethodsThis phase 4, randomised, rater- and sponsor-blinded, prospective, parallel-group, clinic-based head-to-head study was conducted at 43 sites in nine countries. Patients were randomised (1:1) to intravenous natalizumab 300 mg every 4 weeks or oral fingolimod 0.5 mg once daily for ≤52 weeks. Enrolment-related early study termination precluded assessment of the primary endpoint (evolution of new on-treatment gadolinium-enhancing (Gd+) lesions to persistent black holes). Unplanned exploratory analyses of secondary endpoints evaluated the effects of treatment on the development of new T1 Gd+ lesions and new/newly enlarging T2 lesions, lesion volumes and relapse outcomes.ResultsThe intent-to-treat population comprised 108 patients (natalizumab, n=54; fingolimod, n=54); 63 completed ≥24 weeks of treatment. Due to the limited numbers of events and patients at risk, MRI and relapse outcomes were reported over up to 24 and 36 weeks, respectively. The mean number of new T1 Gd+ lesions was numerically lower with natalizumab than with fingolimod by 4 weeks; accumulation rates were 0.02 and 0.09 per week, respectively, over 24 weeks (p=0.004). The cumulative probability of developing ≥1 lesion at 24 weeks was 40.7% with natalizumab versus 58.0% with fingolimod (HR=0.60; 95% CI 0.31–1.16; p=0.126); the corresponding probabilities for ≥2 lesions were 11.5% vs 48.5% (HR=0.25; 95% CI 0.09–0.68; p=0.007). No significant between-group differences were observed for the other MRI outcomes at 24 weeks. The cumulative probability of relapse over follow-up was 1.9% with natalizumab versus 22.3% with fingolimod (HR=0.08; 95% CI 0.01–0.64; p=0.017). Adverse events were consistent with known safety profiles.ConclusionsThese results suggest that natalizumab is more efficacious than fingolimod in reducing multiple sclerosis relapses and T1 Gd+ lesion accumulation in patients with active disease.Trial registration numbersNCT02342704; EUCTR2013-004622-29-IT; Post-results.

scholarly journals 2227. Outcomes in Patients with Renal Impairment from a Phase 3 Clinical Trial for Ceftolozane–Tazobactam (C/T) Treatment of Nosocomial Pneumonia (ASPECT-NP)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S760-S761
Author(s):  
Jennifer A Huntington ◽  
Brian Yu ◽  
Linping Li ◽  
Erin Jensen ◽  
Christopher Bruno ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Impairment ◽  
Nosocomial Pneumonia ◽  
Clinical Cure ◽  
Study Drug ◽  
Double Blind Study ◽  
Phase 3 ◽  
Double Blind ◽  
Intent To Treat ◽  
Cure Rates

Abstract Background ASPECT-NP, a phase 3, randomized, double-blind study, evaluated C/T (at double the approved dose for other indications) vs. meropenem (MEM) in adults with ventilated nosocomial pneumonia. We compared safety and efficacy outcomes from this trial among patients with and without renal impairment (RI). Methods Patients were stratified by age and diagnosis and were randomized 1:1 to intravenous (IV) C/T 3 g every 8 h or IV MEM 1 g every 8 h. Study drug was administered for 8–14 days; doses were adjusted for moderate and severe RI. Eligible patients were mechanically ventilated; those on renal replacement therapy or with creatinine clearance (CrCL) < 15 mL/minute were excluded. Key efficacy endpoints included clinical cure rates at the test of cure (TOC) visit in the intent-to-treat (ITT) and clinically evaluable (CE) populations and Day 28 all-cause mortality (ACM) in the ITT population. In this analysis, patients were stratified based on renal function for outcome comparisons: normal renal function (CrCL ≥ 80 mL/minute); mild RI (CrCL > 50 to < 80 mL/minute); moderate RI (CrCL ≥ 30 to ≤ 50 mL/minute); and severe RI (CrCL ≥ 15 to < 30 mL/minute). Results A total of 726 patients were enrolled (C/T, N = 362; MEM, N = 364). Clinical cure rates at the TOC visit (CE and ITT populations) were robust across CrCL subgroups in both treatment arms and were similar based on 95% confidence intervals for treatment differences that included 0 (table). Day 28 ACM rates for patients with moderate and severe RI were numerically higher than those with mild RI in the MEM treatment arm. Rates of treatment-emergent adverse events (TEAEs) were similar in both treatment arms and across CrCL subgroups, with rates generally increasing with increasing RI severity. Rates of treatment-related TEAEs were low across treatment arms and CrCL subgroups with no treatment-related deaths reported. Conclusion Similar clinical cure and Day 28 ACM rates at the TOC visit were found across treatment groups for all CrCL subgroups, consistent with the overall primary and key secondary efficacy results for the ASPECT-NP study. Both drugs were well-tolerated. The results of this analysis indicate that the use of dose-adjusted C/T is appropriate in patients with nosocomial pneumonia and moderate or severe RI. Disclosures All authors: No reported disclosures.

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