Physical Fitness Training in Patients with Subacute Stroke (PHYS-STROKE): Safety analyses of a randomized clinical trial.

Torsten Rackoll,Agnes Flöel,Martin Ebinger,Alexander H Nave,Ulrike Grittner,Matthias Endres,; For The Phys-Stroke Study Group

doi:10.1177/17474930211006286

Abstract

Background and aimTo report the six-month safety analyses among patients enrolled in the “Physical Fitness Training in Subacute Stroke—PHYS-STROKE” trial and identify underlying risk factors associated with serious adverse events.MethodsWe performed a pre-specified safety analysis of a multicenter, randomized controlled, endpoint-blinded trial comprising 200 patients with moderate to severe subacute stroke (days 5–45 after stroke) that were randomly assigned (1:1) to receive either aerobic, bodyweight supported, treadmill-based training (n = 105), or relaxation sessions (n = 95, control group). Each intervention session lasted for 25 min, five times weekly for four weeks, in addition to standard rehabilitation therapy. Serious adverse events defined as cerebro- and cardiovascular events, readmission to hospital, and death were assessed during six months of follow-up. Incident rate ratios (IRR) were calculated, and Poisson regression analyses were conducted to identify risk factors for serious adverse events and to test the association with aerobic training.ResultsSix months after stroke, 50 serious adverse events occurred in the trial with a higher incidence rate (per 100 patient-months) in the training group compared to the relaxation group (6.31 vs. 3.22; IRR 1.70, 95% CI 0.96 to 3.12). The association of aerobic training with serious adverse events incidence rates were modified by diabetes mellitus (IRR for interaction: 7.10, 95% CI 1.56 to 51.24) and by atrial fibrillation (IRR for interaction: 4.37, 95% CI 0.97 to 31.81).ConclusionsSafety analysis of the PHYS-STROKE trial found a higher rate of serious adverse events in patients randomized to aerobic training compared to control within six months after stroke. Exploratory analyses found an association between serious adverse events occurrence in the aerobic training group with pre-existing diabetes mellitus and atrial fibrillation which should be further investigated in future trials.Data access statementThe raw data and analyses scripts are provided by the authors on a secure online repository for reproduction of reported findings.

Highlights

The number of stroke survivors with impairments is increasing, rendering effective rehabilitation interventions a major unmet medical need.[1]
In accordance with the trial protocol, we report the final safety data of the six-month trial follow-up and provide exploratory analyses aimed to identify patient-related risk factors for serious adverse events (SAE) associated with aerobic training
Patients randomly allocated to the training group were more severely affected than patients in the relaxation group (acute National Institute of Health Stroke Scale (NIHSS): 9 (5–12) vs. 7 (5–11))

Summary

Introduction

The number of stroke survivors with impairments is increasing, rendering effective rehabilitation interventions a major unmet medical need.[1]. Cardiorespiratory stress applied during early rehabilitation might cause adverse effects.[5]. The evidence of safety of aerobic training early after stroke is scarce. The latest Cochrane Collaboration meta-analysis aggregated estimates of adverse effects including cerebro- and cardiovascular events in the stroke population but could not identify a higher risk in aerobic training compared to control interventions.[6] Of note, the evidence derived mainly from small studies with limited reporting of adverse events. To report the six-month safety analyses among patients enrolled in the ‘‘Physical Fitness Training in Subacute Stroke—PHYS-STROKE’’ trial and identify underlying risk factors associated with serious adverse events

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Results

Discussion

Conclusion