scholarly journals Results and lessons learnt from a randomized controlled trial: Prophylactic treatment of vestibular migraine with metoprolol (PROVEMIG)

2019 ◽  
Author(s):  
Otmar Bayer ◽  
Christine Adrion ◽  
Amani Al Tawil ◽  
Ulrich Mansmann ◽  
Michael Strupp
Keyword(s):  
Controlled Trial ◽  
Psychometric Evaluation ◽  
Placebo Treatment ◽  
Vestibular Migraine ◽  
University Hospitals ◽  
Double Blind ◽  
Treatment Benefit ◽  
Episodic Vertigo ◽  
Patient Reported ◽  
Full Analysis

Abstract BACKGROUND Vestibular migraine (VM) is the most frequent cause of recurrent spontaneous attacks of vertigo causally related to migraine. The objective of the PROVEMIG trial was to demonstrate that metoprolol succinate is superior to placebo treatment in the prevention of episodic vertigo- and migraine-related symptoms in patients with VM. METHODS This phase 3, two-arm parallel-group, double-blind, randomized placebo-controlled trial was designed to be conducted at tertiary referral centres at neurology and ENT departments of eight German university hospitals. The planned sample size was a total of 266 patients to be allocated. Adults aged 18 years or above diagnosed with probable or definitive VM according to the Neuhauser criteria 2001 were randomly assigned 1:1 to six months blinded metoprolol (maintenance dosage of 95 mg daily) versus placebo treatment policy. The primary efficacy outcome was the self-reported number of vertiginous attacks per 30 days documented by means of a paper-based daily symptom diary. The pre-specified time period of primary interest was defined within month 4 to 6. Secondary outcomes included the patient-reported number of migraine days and vertigo days, the Dizziness Handicap Inventory and clinical assessments. Adverse events were reported throughout the whole 9-month study period. RESULTS At the time of trial termination, no evidence for a difference in the incidence of vertiginous attacks between both treatment groups was detected. For the full analysis set, the incidence rate ratio (IRR) was 0.983 (95% confidence interval (CI), 0.902 to 1.071) for metoprolol vs. placebo. In both groups, there was a significant decline over time in the overall monthly vertigo attacks by the factor 0.830 (95% CI, 0.776 to 0.887). Results were consistent for all subjective and objective key measures of efficacy. The treatment was well tolerated with no unexpected safety findings. CONCLUSIONS After randomizing 130 patients PROVEMIG had to be discontinued due to poor participant accrual not related to the tolerability of the study medication or safety concerns and no treatment benefit of metoprolol over placebo could be established. Additional preparatory work is much-needed in the development, psychometric evaluation and interpretation of clinically meaningful endpoints in trials on episodic syndromes like VM taking into consideration the complexity of this disease entity comprising of two domains (vertigo- and headache-related disability). TRIAL REGISTRATION EudraCT no 2009-013701-34, prospectively registered on 08 April 2011, https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-013701-34/DE.

scholarly journals Results and lessons learnt from a randomized controlled trial: Prophylactic treatment of vestibular migraine with metoprolol (PROVEMIG)

2019 ◽  
Author(s):  
Otmar Bayer ◽  
Christine Adrion ◽  
Amani Al Tawil ◽  
Ulrich Mansmann ◽  
Michael Strupp
Keyword(s):  
Controlled Trial ◽  
Psychometric Evaluation ◽  
Placebo Treatment ◽  
Vestibular Migraine ◽  
University Hospitals ◽  
Double Blind ◽  
Episodic Vertigo ◽  
Efficacy Outcome ◽  
Patient Reported ◽  
Full Analysis

Abstract BACKGROUND Vestibular migraine (VM) is the most frequent cause of recurrent spontaneous attacks of vertigo causally related to migraine. The objective of the PROVEMIG trial was to demonstrate that metoprolol succinate is superior to placebo treatment in the prevention of episodic vertigo- and migraine-related symptoms in patients with VM. METHODS This phase 3, two-arm parallel-group, double-blind, randomized placebo-controlled trial was designed to be conducted at tertiary referral centres at neurology and ENT departments of eight German university hospitals. The planned sample size was a total of 266 patients to be allocated. Adults aged 18 years or above diagnosed with probable or definitive VM according to the Neuhauser criteria 2001 were randomly assigned 1:1 to six months blinded metoprolol (maintenance dosage of 95 mg daily) versus placebo treatment policy. The primary efficacy outcome was the self-reported number of vertiginous attacks per 30 days documented by means of a paper-based daily symptom diary. The pre-specified time period of primary interest was defined within month 4 to 6. Secondary outcomes included the patient-reported number of migraine days and vertigo days, the Dizziness Handicap Inventory and clinical assessments. Adverse events were reported throughout the whole 9-month study period. RESULTS At the time of trial termination, no evidence for a difference in the incidence of vertiginous attacks between both treatment groups was detected. For the full analysis set, the incidence rate ratio (IRR) was 0.983 (95% confidence interval (CI), 0.902 to 1.071) for metoprolol vs. placebo. There was a significant decline in the overall monthly vertigo attacks by the factor 0.830 (95% CI, 0.776 to 0.887). Results were consistent for all subjective and objective key measures of efficacy. The treatment was well tolerated with no unexpected safety findings. CONCLUSIONS Due to poor participant accrual not related to the tolerability of the study medication or safety concerns PROVEMIG had to be discontinued after randomizing 130 patients. Additional preparatory work is much-needed in the development, psychometric evaluation and interpretation of clinically meaningful endpoints in trials on episodic syndromes like VM taking into consideration the two-dimensional aspect of this disease entity. TRIAL REGISTRATION EudraCT no 2009-013701-34, prospectively registered on 08 April 2011, https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-013701-34/DE.

scholarly journals Results and lessons learnt from a randomized controlled trial: prophylactic treatment of vestibular migraine with metoprolol (PROVEMIG)

Trials ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Otmar Bayer ◽  
◽  
Christine Adrion ◽  
Amani Al Tawil ◽  
Ulrich Mansmann ◽  
...  
Keyword(s):  
Prophylactic Treatment ◽  
Controlled Trial ◽  
Psychometric Evaluation ◽  
Vestibular Migraine ◽  
Phase Iii ◽  
University Hospitals ◽  
Double Blind ◽  
Treatment Benefit ◽  
Episodic Vertigo ◽  
Patient Reported

Abstract Background Vestibular migraine (VM) is the most frequent cause of recurrent spontaneous attacks of vertigo causally related to migraine. The objective of the Prophylactic treatment of vestibular migraine with metoprolol (PROVEMIG) trial was to demonstrate that metoprolol succinate is superior to placebo in the prevention of episodic vertigo- and migraine-related symptoms in patients with VM. Methods This phase III, two-arm, parallel-group, double-blind, randomized placebo-controlled trial was designed to be conducted at tertiary referral centres at neurology and ear, nose and throat departments of eight German university hospitals. The planned sample size was a total of 266 patients to be allocated. Adults aged 18 years or above diagnosed with probable or definitive VM according to the Neuhauser criteria 2001 were randomly assigned 1:1 to 6 months blinded metoprolol (maintenance dosage of 95 mg daily) or placebo. The primary efficacy outcome was the self-reported number of vertiginous attacks per 30 days documented by means of a paper-based daily symptom diary. The pre-specified time period of primary interest was defined as months 4 to 6. Secondary outcomes included the patient-reported number of migraine days and vertigo days, the Dizziness Handicap Inventory, and clinical assessments. Adverse events were reported throughout the whole 9-month study period. Results At the time of trial termination, no evidence for a difference in the incidence of vertiginous attacks between groups was detected. For the full analysis set, the incidence rate ratio was 0.983 (95% confidence interval (CI) 0.902–1.071) for metoprolol versus placebo. In both groups, there was a significant decline over time in the overall monthly vertigo attacks by a factor of 0.830 (95% CI 0.776–0.887). Results were consistent for all subjective and objective key measures of efficacy. The treatment was well tolerated with no unexpected safety findings. Conclusions After randomizing 130 patients PROVEMIG had to be discontinued because of poor participant accrual not related to the tolerability of the study medication or safety concerns; no treatment benefit of metoprolol over placebo could be established. Additional preparatory work is much needed in the development, psychometric evaluation and interpretation of clinically meaningful end points in trials on episodic syndromes like VM taking into consideration the complexity of this disease entity comprising two domains (vertigo- and headache-related disability). Trial registration EudraCT, 2009-013701-34. Prospectively registered on 8 April 2011.

Clinical and attentional effects of acute nicotine treatment in Tourette’s syndrome

2004 ◽  
Vol 19 (2) ◽  
pp. 102-112 ◽  
Author(s):  
Anne L. Howson ◽  
Sue Batth ◽  
Vadim Ilivitsky ◽  
Armand Boisjoli ◽  
Martine Jaworski ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Event Related Potentials ◽  
Placebo Treatment ◽  
Tourette's Syndrome ◽  
Tourette’S Syndrome ◽  
Continuous Performance Task ◽  
Open Label ◽  
Double Blind ◽  
Nicotine Treatment ◽  
Related Potentials

AbstractEvidence from pre-clinical infrahuman investigations, open-label clinical trials, and a single controlled trial found acute nicotine treatment potentiated up to 4 weeks neuroleptic-induced reductions of dyskinetic symptoms characterizing Tourette’s syndrome (TS). Given the attentional disturbances associated with this syndrome, and the improvements in attentional processes reported with nicotine, this randomized, double-blind, placebo-controlled trial examined the acute (4 h) and sustained (2 weeks) effects of a single dose of transdermal nicotine on clinical (i.e., tics), attentional (continuous performance task, event-related potentials, patient and parental reports) and behavioral symptoms in 23 children and adolescents with TS receiving neuroleptic treatment. In the 14 evaluable patients with complete primary efficacy data, nicotine (compared to placebo) failed to alter symptoms at 4 h but counteracted ERP-P300 signs of diminished attention seen 2 weeks following placebo treatment. Secondary efficacy measures, including patient self-reports and parental ratings, found nicotine to reduce complex tics and improve behaviors related to inattention. Additional work with intermittent dosing schedules is required to characterize optimal clinical and cognitive effects with nicotine treatment.

scholarly journals A Randomized Controlled Trial of the Efficacy of Systemic Enzymes and Probiotics in the Resolution of Post-COVID Fatigue

Medicines ◽  
2021 ◽  
Vol 8 (9) ◽  
pp. 47
Author(s):  
Abhijit Rathi ◽  
Swati B. Jadhav ◽  
Neha Shah
Keyword(s):  
Treatment Efficacy ◽  
Controlled Trial ◽  
Placebo Treatment ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Time Points ◽  
Randomized Controlled ◽  
Cognitive Disturbances ◽  
Oral Supplements

Muscle fatigue and cognitive disturbances persist in patients after recovery from acute COVID-19 disease. However, there are no specific treatments for post-COVID fatigue. Objective: To evaluate the efficacy and safety of the health supplements ImmunoSEB (systemic enzyme complex) and ProbioSEB CSC3 (probiotic complex) in patients suffering from COVID-19 induced fatigue. A randomized, multicentric, double blind, placebo-controlled trial was conducted in 200 patients with a complaint of post-COVID fatigue. The test arm (n = 100) received the oral supplements for 14 days and the control arm (n = 100) received a placebo. Treatment efficacy was compared using the Chalder Fatigue scale (CFQ-11), at various time points from days 1 to 14. The supplemental treatment resulted in resolution of fatigue in a greater percentage of subjects in the test vs. the control arm (91% vs. 15%) on day 14. Subjects in the test arm showed a significantly greater reduction in total as well as physical and mental fatigue scores at all time points vs. the control arm. The supplements were well tolerated with no adverse events reported. This study demonstrates that a 14 days supplementation of ImmunoSEB + ProbioSEB CSC3 resolves post-COVID-19 fatigue and can improve patients’ functional status and quality of life.

scholarly journals Efficacy and Safety of Jueyin Granules for Patients with Mild-to-Moderate Psoriasis Vulgaris: Protocol for a Multicenter Randomized Placebo-Controlled Trial

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Su Li ◽  
Cang Zhang ◽  
Hong-Ya Zhang ◽  
Meng Zhou ◽  
Si-Nong Wang ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Life Quality ◽  
Severity Index ◽  
Placebo Treatment ◽  
International Standards ◽  
Physician Global Assessment ◽  
Double Blind ◽  
Objective Evidence ◽  
Multicenter Randomized Controlled Trial ◽  
Heat Syndrome

Introduction. The etiology and pathogenesis of psoriasis are complex. Blood-heat syndrome is the core pathogenesis of psoriasis. Based on theories of Chinese medicine (CM), heat-clearing and blood-cooling (HCBC) are the primary treatment. Very few studies have investigated the pharmacological mechanism of the CM HCBC method for treating psoriasis. This multicenter randomized controlled trial will focus on treating psoriasis blood-heat syndrome with the HCBC method using Jueyin granules (JYKL). This will be an objective and standardized evaluation of the efficacy, safety, and reproducibility of the HCBC method to obtain objective evidence meeting international standards that aim to establish a clinical standard suitable for the popular application of CM for treating psoriasis. Methods and Analysis. A five-center randomized double-blind placebo-controlled clinical design will be used in this study. At least 196 participants will be randomly assigned to receive either JYKL or placebo treatment approximately 30 minutes after meals in the morning and evening (one sachet per time, twice daily for 8 consecutive weeks). The study duration will be 17 weeks, including 1 week of screening, 8 weeks of intervention, and 8 weeks of follow-up. The patients will be evaluated every 2 weeks, and the measures will be compared with baseline values. The primary outcome measure will be the psoriasis lesion area severity index. We will also observe the recurrence rate, body surface area, physician global assessment, dermatology life quality index, quality of life index, visual analogue scale score, CM symptom score, combined drug use, and adverse events. This trial is registered with NCT03961230.

scholarly journals Efficacy and safety of abatacept in active primary Sjögren’s syndrome: results of a phase III, randomised, placebo-controlled trial

2020 ◽  
pp. annrheumdis-2020-218599
Author(s):  
Alan N Baer ◽  
Jacques-Eric Gottenberg ◽  
E William St Clair ◽  
Takayuki Sumida ◽  
Tsutomu Takeuchi ◽  
...  
Keyword(s):  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Controlled Trial ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Phase Iii ◽  
Open Label ◽  
Double Blind ◽  
Patient Reported ◽  
Sjögren‘S Syndrome

ObjectivesTo evaluate efficacy and safety of abatacept in adults with active primary Sjögren’s syndrome (pSS) in a phase III, randomised, double-blind, placebo-controlled trial.MethodsEligible patients (moderate-to-severe pSS [2016 ACR/European League Against Rheumatism (EULAR) criteria], EULAR Sjögren’s Syndrome Disease Activity Index [ESSDAI] ≥5, anti-SS-related antigen A/anti-Ro antibody positive) received weekly subcutaneous abatacept 125 mg or placebo for 169 days followed by an open-label extension to day 365. Primary endpoint was mean change from baseline in ESSDAI at day 169. Key secondary endpoints were mean change from baseline in EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) and stimulated whole salivary flow (SWSF) at day 169. Other secondary clinical endpoints included glandular functions and patient-reported outcomes. Selected biomarkers and immune cell phenotypes were examined. Safety was monitored.ResultsOf 187 patients randomised, 168 completed double-blind period and 165 continued into open-label period. Mean (SD) baseline ESSDAI and ESSPRI total scores were 9.4 (4.3) and 6.5 (2.0), respectively. Statistical significance was not reached for primary (ESSDAI −3.2 abatacept vs −3.7 placebo, p=0.442) or key secondary endpoints (ESSPRI, p=0.337; SWSF, p=0.584). No clinical benefit of abatacept over placebo at day 169 was seen with other clinical and PRO endpoints. Relative to baseline, abatacept was associated with significant differences vs placebo in some disease-relevant biomarkers (including IgG, IgA, IgM-rheumatoid factor) and pathogenic cell subpopulations (post hoc analyses). No new safety signals were identified.ConclusionsAbatacept treatment did not result in significant clinical efficacy compared with placebo in patients with moderate-to-severe pSS, despite evidence of biological activity.

Changes in patient-reported outcomes in women with breast cancer in a multicenter double-blind randomized controlled trial assessing the effect of acupuncture in reducing aromatase inhibitor-induced musculoskeletal symptoms (AIMSS).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9103-9103
Author(s):  
Ting Bao ◽  
Kelly Betts ◽  
Karineh Tarpinian ◽  
Ling Cai ◽  
Jeff Gould ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Controlled Trial ◽  
Depression Scale ◽  
Sham Acupuncture ◽  
Menopausal Symptoms ◽  
Musculoskeletal Symptoms ◽  
Double Blind ◽  
Hot Flash ◽  
Significant Difference ◽  
Patient Reported

9103 Background: Aromatase Inhibitors (AIs) have been associated with worsening of patient related outcomes (PROs) such as AIMSS, menopausal symptoms and depression. Acupuncture has been reported to alleviate such symptoms. We hypothesized that real acupuncture (RA) would improve PROs more than sham acupuncture (SA). Methods: We collected PROs at baseline, 4, 8, and 12 weeks (wks), from women enrolled in a multi-center double blind RCT designed to assess the effect of acupuncture in reducing PROs. Patients were randomized to 8 wkly RA or SA. PROs were measured by the revised National Surgical Adjuvant Breast and Bowel Project (NSABP) menopausal symptoms questionnaire, Center for Epidemiological Studies Depression Scale (CESD), Hospital Anxiety and Depression Scale (HADS), Pittsburgh Sleep Quality Index (PSQI), Hot Flash Daily Diary, Hot Flash Related Daily Interference Scale (HFRDI) and EuroQoL survey. We measured estrogen and cytokines concentrations at baseline and wk 8. We used Wilcoxon rank sum and signed-rank tests to make comparisons between and within group, respectively. Results: We included 23 patients from RA and 24 from SA arms in the intent-to-treat analysis. We have previously reported no significant difference in reduction of AIMSS between two arms. RA caused reduction of CESD scores compared to SA (median: -2 vs 0, p = 0.057). When compared to baseline, there were statistically significant improvements at wk 8 in hot flash severity score (p=0.006), hot flash frequency (p=0.011), HFRDI (p=0.014) and NSABP menopausal symptoms (p=0.022) scores in RA arm; for EuroQoL (p=0.022), HFRDI (p=0.043) and NSABP menopausal symptoms (p=0.005) scores in SA arm. The majority of patients’ estradiol concentrations were undetectable at baseline and wk 8. Changes in other time points, data and analysis of cytokines changes will be presented at the meeting. Conclusions: Real and sham acupuncture were both associated with improvement in PROs in breast cancer patients taking AIs. We detected no significant difference in the change of PROs between real and sham acupuncture, except for CESD.

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