P.3.c.053 Relating reported extrapyramidal adverse events to movement disorder rating scales in ziprasidone randomised clinical trials

ObjectiveTo determine the impact of ivabradine on outcomes important to patients with angina pectoris caused by coronary artery disease.MethodsWe conducted a systematic review. We included randomised clinical trials comparing ivabradine versus placebo or no intervention for patients with angina pectoris due to coronary artery disease published prior to June 2020. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, Cochrane methodology, Trial Sequential Analysis, Grading of Recommendations Assessment, Development, and Evaluation, and our eight-step procedure. Primary outcomes were all-cause mortality, serious adverse events and quality of life.ResultsWe included 47 randomised clinical trials enrolling 35 797 participants. All trials and outcomes were at high risk of bias. Ivabradine compared with control did not have effects when assessing all-cause mortality (risk ratio [RR] 1.04; 95% CI 0.96 to 1.13), quality of life (standardised mean differences −0.05; 95% CI −0.11 to 0.01), cardiovascular mortality (RR 1.07; 95% CI 0.97 to 1.18) and myocardial infarction (RR 1.03; 95% CI 0.91 to 1.16). Ivabradine seemed to increase the risk of serious adverse events after removal of outliers (RR 1.07; 95% CI 1.03 to 1.11) as well as the following adverse events classified as serious: bradycardia, prolonged QT interval, photopsia, atrial fibrillation and hypertension. Ivabradine also increased the risk of non-serious adverse events (RR 1.13; 95% CI 1.11 to 1.16). Ivabradine might have a statistically significant effect when assessing angina frequency (mean difference (MD) 2.06; 95% CI 0.82 to 3.30) and stability (MD 1.48; 95% CI 0.07 to 2.89), but the effect sizes seemed minimal and possibly without any relevance to patients, and we identified several methodological limitations, questioning the validity of these results.ConclusionOur findings do not support that ivabradine offers significant benefits on patient important outcomes, but rather seems to increase the risk of serious adverse events such as atrial fibrillation and non-serious adverse events. Based on current evidence, guidelines need reassessment and the use of ivabradine for angina pectoris should be reconsidered.PROSPERO registration numberCRD42018112082.

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Information on adverse events in randomised clinical trials assessing drug interventions published in four medical journals with high impact factors

International Journal of Risk & Safety in Medicine ◽

10.3233/jrs-140609 ◽

2014 ◽

Vol 26 (1) ◽

pp. 9-22 ◽

Cited By ~ 9

Author(s):

Cátia Bauer Maggi ◽

Isabel Heinzmann Griebeler ◽

Tatiane da Silva Dal Pizzol

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

High Impact ◽

Randomised Clinical Trials ◽

Impact Factors ◽

Medical Journals ◽

Drug Interventions

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Efficacy and safety of diosmectite in acute childhood diarrhoea: a meta-analysis

Archives of Disease in Childhood ◽

10.1136/archdischild-2014-307632 ◽

2015 ◽

Vol 100 (7) ◽

pp. 704-712 ◽

Cited By ~ 17

Author(s):

Rashmi Ranjan Das ◽

Jhuma Sankar ◽

Sushree Samiksha Naik

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Outcome Measures ◽

Meta Analysis ◽

Acute Diarrhoea ◽

Randomised Clinical Trials ◽

Secondary Outcome ◽

Future Research ◽

Open Label ◽

Childhood Diarrhoea

ObjectiveWe evaluated the role of diosmectite as an add-on treatment to the ‘recommended treatment’ of acute diarrhoea in children.MethodsWe searched all published literature through the major databases: Medline via Ovid, PubMed, CENTRAL, Embase and Google Scholar till May 2014. Randomised clinical trials comparing diosmectite versus placebo were included (PROSPERO registration: CRD42014013783).Main outcome measuresThe primary outcome measures were duration of acute diarrhoea (h), and day-to-day cure rates (%). The secondary outcome measures were stool output (volume), stool output (frequency) and adverse events.ResultsOf 384 citations retrieved, a total of 13 randomised clinical trials (2164 children, 1–60 months old) were included in the meta-analysis. A dose of 3–6 grams per day of diosmectite was given for a duration from 3 days until recovery. Compared with placebo, diosmectite significantly decreased the duration of acute diarrhoea (mean difference, −23.39; 95% CI −28.77 to −18.01), and increased the cure rate (%) at day 5 (OR, 4.44; 95% CI 1.66 to 11.84), without any increases in the risk of adverse events. Diosmectite was effective in all types of acute childhood diarrhoea except dysentery. Because, most of the trials were open-label, and there was a high possibility of publication bias, the GRADE evidence generated was of ‘low quality’.ConclusionsDiosmectite may be a useful additive in the treatment of acute childhood diarrhoea. As the evidence generated was of ‘low quality’, future research is needed with higher quality designs before any firm recommendations can be made.Trial registration numberPROSPERO registration: CRD42014013783.

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