Fampridine and Acetazolamide in EA2 and Related Familial EA: A Prospective Randomized Placebo-controlled Trial

2020 ◽  
pp. 10.1212/CPJ.0000000000001017
Author(s):  
Carolin Muth ◽  
Julian Teufel ◽  
Ludger Schöls ◽  
Matthis Synofzik ◽  
Christiana Franke ◽  
...  
Keyword(s):  
Crossover Trial ◽  
Controlled Trial ◽  
Random Sequence ◽  
Positive Family History ◽  
Phase Iii ◽  
Prolonged Release ◽  
Taste Disturbance ◽  
Double Blind ◽  
Episodic Ataxia Type 2 ◽  
Gastrointestinal Complaints

AbstractObjectiveWe determine the efficacy and safety of the treatment with prolonged-release 4-aminopyridine (fampridine) and acetazolamide for patients with episodic ataxia type 2 (EA2). Therefore, 30 patients with EA2 were treated with a random sequence of fampridine, acetazolamide, and placebo in a three-period crossover trial.MethodsA total of 30 patients with EA2 (eight female; aged 20-71 years; 18 genetically confirmed, four with a positive family history, eight with the clinical diagnosis) were enrolled in this phase III, randomised, double-blind, placebo-controlled, three-period crossover trial. Each period lasted 12 weeks with a four-week washout-period. Each patient received a random sequence of 20 mg/d fampridine, 750 mg/d acetazolamide, and placebo. The primary endpoint was the number of attacks during the last 30 days within the 12-week treatment-period. Participants, caregivers, and those assessing the outcomes were blinded to the intervention.ResultsCompared to placebo, fampridine reduced the number of attacks to 63% (95% CI 54% - 74%) and acetazolamide to 52% (95% CI 46% - 60%). A total of 39 (26.5%) adverse events were observed under treatment with fampridine (mostly tingling paraesthesia, and fatigue), 66 (44.9%) happened under acetazolamide (mostly taste disturbance, gastrointestinal complaints), and 42 (28.6%) under placebo (mostly gastrointestinal complaints).ConclusionBoth fampridine and acetazolamide significantly reduce the number of attacks in patients with EA2 and related EA in comparison to placebo. Fampridine 10 mg twice daily had fewer side effects than acetazolamide 250 mg three times daily.

Brivanib in Patients With Advanced Hepatocellular Carcinoma Who Were Intolerant to Sorafenib or for Whom Sorafenib Failed: Results From the Randomized Phase III BRISK-PS Study

2013 ◽  
Vol 31 (28) ◽  
pp. 3509-3516 ◽  
Author(s):  
Josep M. Llovet ◽  
Thomas Decaens ◽  
Jean-Luc Raoul ◽  
Eveline Boucher ◽  
Masatoshi Kudo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Controlled Trial ◽  
Objective Response ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Time To Progression ◽  
Fibroblast Growth Factor Receptors ◽  
Double Blind ◽  
Dual Inhibitor

Purpose Brivanib is a selective dual inhibitor of vascular endothelial growth factor and fibroblast growth factor receptors implicated in tumorigenesis and angiogenesis in hepatocellular carcinoma (HCC). An unmet medical need persists for patients with HCC whose tumors do not respond to sorafenib or who cannot tolerate it. This multicenter, double-blind, randomized, placebo-controlled trial assessed brivanib in patients with HCC who had been treated with sorafenib. Patients and Methods In all, 395 patients with advanced HCC who progressed on/after or were intolerant to sorafenib were randomly assigned (2:1) to receive brivanib 800 mg orally once per day plus best supportive care (BSC) or placebo plus BSC. The primary end point was overall survival (OS). Secondary end points included time to progression (TTP), objective response rate (ORR), and disease control rate based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) and safety. Results Median OS was 9.4 months for brivanib and 8.2 months for placebo (hazard ratio [HR], 0.89; 95.8% CI, 0.69 to 1.15; P = .3307). Adjusting treatment effect for baseline prognostic factors yielded an OS HR of 0.81 (95% CI, 0.63 to 1.04; P = .1044). Exploratory analyses showed a median time to progression of 4.2 months for brivanib and 2.7 months for placebo (HR, 0.56; 95% CI, 0.42 to 0.76; P < .001), and an mRECIST ORR of 10% for brivanib and 2% for placebo (odds ratio, 5.72). Study discontinuation due to treatment-related adverse events (AEs) occurred in 61 brivanib patients (23%) and nine placebo patients (7%). The most frequent treatment-related grade 3 to 4 AEs for brivanib included hypertension (17%), fatigue (13%), hyponatremia (11%), and decreased appetite (10%). Conclusion In patients with HCC who had been treated with sorafenib, brivanib did not significantly improve OS. The observed benefit in the secondary outcomes of TTP and ORR warrants further investigation.

scholarly journals Melatonin for prevention of postoperative delirium after lower limb fracture surgery in elderly patients (DELIRLESS): study protocol for a multicentre randomised controlled trial

BMJ Open ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. e053908
Author(s):  
Stéphanie Sigaut ◽  
Camille Couffignal ◽  
Marina Esposito-Farèse ◽  
Vincent Degos ◽  
Serge Molliex ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Lower Limb ◽  
Postoperative Delirium ◽  
Controlled Trial ◽  
Functional Decline ◽  
Assessment Method ◽  
Phase Iii ◽  
Double Blind ◽  
Prolonged Length ◽  
Surgery In Elderly

IntroductionPostoperative delirium (POD) is one of the most frequent complication after surgery in elderly patients, and is associated with increased morbidity and mortality, prolonged length of stay, cognitive and functional decline leading to loss of autonomy, and important additional healthcare costs. Perioperative inflammatory stress is a key element in POD genesis. Melatonin exhibits antioxidative and immune-modulatory proprieties that are promising concerning delirium prevention, but in perioperative context literature are scarce and conflicting. We hypothesise that perioperative melatonin can reduce the incidence of POD.Methods and analysisThe DELIRLESS trial is a prospective, national multicentric, phase III, superiority, comparative randomised (1:1) double-blind clinical trial. Among patients aged 70 or older, hospitalised and scheduled for surgery of a severe fracture of a lower limb, 718 will be randomly allocated to receive either melatonin 4 mg per os or placebo, every night from anaesthesiologist preoperative consultation and up to 5 days after surgery. The primary outcome is POD incidence measured by either the French validated translation of the Confusion Assessment Method (CAM) score for patients hospitalised in surgery, or CAM-ICU score for patients hospitalised in ICU (Intensive Care Unit). Daily delirium assessment will take place during 10 days after surgery, or until the end of hospital stay if it is shorter. POD cumulative incidence function will be compared at day 10 between the two randomised arms in a competing risks framework, using the Fine and Grey model with death as a competing risk of delirium.Ethics and disseminationThe DELIRLESS trial has been approved by an independent ethics committee the Comité de Protection des Personnes (CPP) Sud-Est (ref CPP2020-18-99 2019-003210-14) for all study centres. Participant recruitment begins in December 2020. Results will be published in international peer-reviewed medical journals.Trial registration numberNCT04335968, first posted 7 April 2020.Protocol version identifierN°3–0, 3 May 2021.

scholarly journals Efficacy and Safety of 5-Fluorouracil 0.5%/Salicylic Acid 10% in the Field-Directed Treatment of Actinic Keratosis: A Phase III, Randomized, Double-Blind, Vehicle-Controlled Trial

2016 ◽  
Vol 7 (1) ◽  
pp. 81-96 ◽  
Author(s):  
Eggert Stockfleth ◽  
Ralph von Kiedrowski ◽  
Rolf Dominicus ◽  
John Ryan ◽  
Adam Ellery ◽  
...  
Keyword(s):  
Salicylic Acid ◽  
Actinic Keratosis ◽  
Controlled Trial ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Double Blind

Economic Analysis of Tirilazad Mesylate for Aneurysmal Subarachnoid Hemorrhage: Economic Evaluation of a Phase III Clinical Trial in Europe and Australia

1998 ◽  
Vol 14 (1) ◽  
pp. 145-160 ◽  
Author(s):  
Henry Glick ◽  
Richard Willke ◽  
Daniel Polsky ◽  
Ted Llana ◽  
Wayne M. Alves ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cost Effectiveness ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Controlled Trial ◽  
Cost Of Care ◽  
Phase Iii ◽  
Double Blind ◽  
Additional Information ◽  
Tirilazad Mesylate ◽  
The Cost

AbstractThis study used data from a multinational phase III randomized, double-blind, vehicle-controlled trial to evaluate the cost-effectiveness of tirilazad mesylate (Freedox®) in the treatment of aneurysmal subarachnoid hemorrhage. In men, therapy with 6 mg/kg per day of tirilazad mesylate was associated with significantly increased survival, increased cost of care, and ratios of cost per death averted that compare favorably with the ratios of other life and death interventions. In women, it appeared to have no effects on costs or survival. Further clinical studies may provide additional information about the cost-effectiveness of this intervention.

A Controlled Trial of Baclofen in Children with Cerebral Palsy

1973 ◽  
Vol 1 (2) ◽  
pp. 398-404 ◽  
Author(s):  
P J Milla ◽  
A D M Jackson
Keyword(s):  
Cerebral Palsy ◽  
Side Effects ◽  
Dose Reduction ◽  
Crossover Trial ◽  
Controlled Trial ◽  
Drug Effects ◽  
Double Blind ◽  
Muscle Spasticity ◽  
Children With Cerebral Palsy ◽  
Better Than

A double-blind crossover trial against placebo was conducted to assess the effects of the GABA derivative, baclofen, on the disabilities due to muscle spasticity in twenty children suffering from cerebral palsy. Baclofen performed very significantly better than placebo in reducing spasticity and significantly better than placebo in allowing both active and passive limb movements to be carried out. Notable improvement was also seen in scissoring. Side-effects were minimal and responded promptly to dose reduction. The evaluation of drug effects on muscle spasticity and the pharmacodynamics of baclofen are discussed. Recommendations are made regarding dosage of baclofen in childhood.

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