1. Home
  2. randomized controlled trial

randomized controlled trial

Outpatient randomized controlled trials to reduce COVID-19 hospitalization: Systematic review and meta-analysis

Author/s: 
Daniele Focosi, David J. Sullivan, Daniel F. Hanley, Mario Cruciani, Massimo Franchini, Jiangda Ou, Arturo Casadevall, Nigel Paneth

This COVID-19 outpatient randomized controlled trials (RCTs) systematic review compares hospitalization outcomes amongst four treatment classes over pandemic period, geography, variants, and vaccine status. Outpatient RCTs with hospitalization endpoint were identified in Pubmed searches through May 2023, excluding RCTs <30 participants (PROSPERO-CRD42022369181). Risk of bias was extracted from COVID-19-NMA, with odds ratio utilized for pooled comparison. Searches identified 281 studies with 61 published RCTs for 33 diverse interventions analyzed. RCTs were largely unvaccinated cohorts with at least one COVID-19 hospitalization risk factor. Grouping by class, monoclonal antibodies (mAbs) (OR = 0.31 [95% CI = 0.24-0.40]) had highest hospital reduction efficacy, followed by COVID-19 convalescent plasma (CCP) (OR = 0.69 [95% CI = 0.53-0.90]), small molecule antivirals (OR = 0.78 [95% CI = 0.48-1.33]), and repurposed drugs (OR = 0.82 [95% CI: 0.72-0.93]). Earlier in disease onset interventions performed better than later. This meta-analysis allows approximate head-to-head comparisons of diverse outpatient interventions. Omicron sublineages (XBB and BQ.1.1) are resistant to mAbs Despite trial heterogeneity, this pooled comparison by intervention class indicated oral antivirals are the preferred outpatient treatment where available, but intravenous interventions from convalescent plasma to remdesivir are also effective and necessary in constrained medical resource settings or for acute and chronic COVID-19 in the immunocompromised.

Keywords 
COVID-19 convalescent plasma monoclonal antibody outpatients randomized controlled trial small molecule antivirals

Effect of Stenting Plus Medical Therapy vs Medical Therapy Alone on Risk of Stroke and Death in Patients With Symptomatic Intracranial Stenosis The CASSISS Randomized Clinical Trial

Author/s: 
Gao, P., Wang, T., Wang, D., Liebeskind, D. S.", H., Li, T., Zhao, Z., Cai, Y., Wu, W., He, W., Yu, J., Zheng, B., Wang, H., Wu, Y., Dmytriw, A. A., Krings, T., Derdeyn, C. P., Jiao, L., CASSISS Trial Investigators

Importance: Prior randomized trials have generally shown harm or no benefit of stenting added to medical therapy for patients with symptomatic severe intracranial atherosclerotic stenosis, but it remains uncertain as to whether refined patient selection and more experienced surgeons might result in improved outcomes.

Objective: To compare stenting plus medical therapy vs medical therapy alone in patients with symptomatic severe intracranial atherosclerotic stenosis.

Design, setting, and participants: Multicenter, open-label, randomized, outcome assessor-blinded trial conducted at 8 centers in China. A total of 380 patients with transient ischemic attack or nondisabling, nonperforator (defined as nonbrainstem or non-basal ganglia end artery) territory ischemic stroke attributed to severe intracranial stenosis (70%-99%) and beyond a duration of 3 weeks from the latest ischemic symptom onset were recruited between March 5, 2014, and November 10, 2016, and followed up for 3 years (final follow-up: November 10, 2019).

Interventions: Medical therapy plus stenting (n = 176) or medical therapy alone (n = 182). Medical therapy included dual-antiplatelet therapy for 90 days (single antiplatelet therapy thereafter) and stroke risk factor control.

Main outcomes and measures: The primary outcome was a composite of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. There were 5 secondary outcomes, including stroke in the qualifying artery territory at 2 years and 3 years as well as mortality at 3 years.

Results: Among 380 patients who were randomized, 358 were confirmed eligible (mean age, 56.3 years; 263 male [73.5%]) and 343 (95.8%) completed the trial. For the stenting plus medical therapy group vs medical therapy alone, no significant difference was found for the primary outcome of risk of stroke or death (8.0% [14/176] vs 7.2% [13/181]; difference, 0.4% [95% CI, -5.0% to 5.9%]; hazard ratio, 1.10 [95% CI, 0.52-2.35]; P = .82). Of the 5 prespecified secondary end points, none showed a significant difference including stroke in the qualifying artery territory at 2 years (9.9% [17/171] vs 9.0% [16/178]; difference, 0.7% [95% CI, -5.4% to 6.7%]; hazard ratio, 1.10 [95% CI, 0.56-2.16]; P = .80) and 3 years (11.3% [19/168] vs 11.2% [19/170]; difference, -0.2% [95% CI, -7.0% to 6.5%]; hazard ratio, 1.00 [95% CI, 0.53-1.90]; P > .99). Mortality at 3 years was 4.4% (7/160) in the stenting plus medical therapy group vs 1.3% (2/159) in the medical therapy alone group (difference, 3.2% [95% CI, -0.5% to 6.9%]; hazard ratio, 3.75 [95% CI, 0.77-18.13]; P = .08).

Conclusions and relevance: Among patients with transient ischemic attack or ischemic stroke due to symptomatic severe intracranial atherosclerotic stenosis, the addition of percutaneous transluminal angioplasty and stenting to medical therapy, compared with medical therapy alone, resulted in no significant difference in the risk of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. The findings do not support the addition of percutaneous transluminal angioplasty and stenting to medical therapy for the treatment of patients with symptomatic severe intracranial atherosclerotic stenosis.

Trial registration: ClinicalTrials.gov Identifier: NCT01763320.

Keywords 
randomized controlled trial Multicenter Study Treatment Outcome Pathologic Constriction stroke Stent

Effect of Physical Therapy vs Arthroscopic Partial Meniscectomy in People With Degenerative Meniscal Tears: Five-Year Follow-up of the ESCAPE Randomized Clinical Trial

Author/s: 
Noorduyn, J. C. A., Van de Graaf, V. A., Willigenburg, N. W., Scholten-Peeters, G. G. M., Kret, Kret, E. J., Van Dijk, R. A., Buchbinder, R., Hawker, G. A., Coppieters, M. W., Poolman, R. W., ESCAPE Research Group

Importance: There is a paucity of high-quality evidence about the long-term effects (ie, 3-5 years and beyond) of arthroscopic partial meniscectomy vs exercise-based physical therapy for patients with degenerative meniscal tears.

Objectives: To compare the 5-year effectiveness of arthroscopic partial meniscectomy and exercise-based physical therapy on patient-reported knee function and progression of knee osteoarthritis in patients with a degenerative meniscal tear.

Design, setting, and participants: A noninferiority, multicenter randomized clinical trial was conducted in the orthopedic departments of 9 hospitals in the Netherlands. A total of 321 patients aged 45 to 70 years with a degenerative meniscal tear participated. Data collection took place between July 12, 2013, and December 4, 2020.

Interventions: Patients were randomly allocated to arthroscopic partial meniscectomy or 16 sessions of exercise-based physical therapy.

Main outcomes and measures: The primary outcome was patient-reported knee function (International Knee Documentation Committee Subjective Knee Form (range, 0 [worst] to 100 [best]) during 5 years of follow-up based on the intention-to-treat principle, with a noninferiority threshold of 11 points. The secondary outcome was progression in knee osteoarthritis shown on radiographic images in both treatment groups.

Results: Of 321 patients (mean [SD] age, 58 [6.6] years; 161 women [50.2%]), 278 patients (87.1%) completed the 5-year follow-up with a mean follow-up time of 61.8 months (range, 58.8-69.5 months). From baseline to 5-year follow-up, the mean (SD) improvement was 29.6 (18.7) points in the surgery group and 25.1 (17.8) points in the physical therapy group. The crude between-group difference was 3.5 points (95% CI, 0.7-6.3 points; P < .001 for noninferiority). The 95% CI did not exceed the noninferiority threshold of 11 points. Comparable rates of progression of radiographic-demonstrated knee osteoarthritis were noted between both treatments.

Conclusions and relevance: In this noninferiority randomized clinical trial after 5 years, exercise-based physical therapy remained noninferior to arthroscopic partial meniscectomy for patient-reported knee function. Physical therapy should therefore be the preferred treatment over surgery for degenerative meniscal tears. These results can assist in the development and updating of current guideline recommendations about treatment for patients with a degenerative meniscal tear.

Trial registration: ClinicalTrials.gov Identifier: NCT01850719.

Keywords 
Knee Injuries Follow-Up Studies randomized controlled trial Meniscus Injuries Meniscectomy

Tai Chi for Chronic Illness Management: Synthesizing Current Evidence from Meta-Analyses of Randomized Controlled Trials

Author/s: 
Zou, Liye, Xiao, Tao, Cao, Chao, Smith, Lee, Imm, Kellie, Grabovac, Igor, Waldhoer, Thomas

An umbrella review of systematic reviews and meta-analyses of randomized controlled trials (RCTs) was conducted to evaluate the existing evidence of Tai Chi as a mind-body exercise for chronic illness management. MEDLINE/PubMed and Embase databases were searched from inception until 31st March 2019 for meta-analyses of at least two RCTs that investigated health outcomes associated with Tai Chi intervention. Evidence of significant outcomes (P-value <0.05) was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. This review identified 45 meta-analyses of RCTs and calculated 142 summary estimates among adults living with 16 types of chronic illnesses. Statistically significant results (P-value <0.05) were identified for 81 of the 142 outcomes (57.0%), of which 45 estimates presenting 30 unique outcomes across 14 chronic illnesses were supported by high (n=1) or moderate (n=44) evidence. Moderate evidence suggests that Tai Chi intervention improved physical functions and disease-specific outcomes compared with non-active controls and cardiorespiratory fitness compared with active controls among adults with diverse chronic illnesses. Between-study heterogeneity and publication bias were observed in some meta-analyses.

Keywords 
Tai Chi chronic Illness mind-body exercise randomized controlled trial umbrella review
Subscribe to randomized controlled trial