Placebo treatment in acute stroke trials - Benefit or harm to patients?

Background and Purpose-Some stroke patients and their families express rese rvations about participating in trials of experimental therapies for acute stroke. Among many reasons given for this is the concern that by participat ing, patients may be deprived of some component of routine care. We sought to determine the effect on outcome of participating in a clinical stroke tr ial while being treated with placebo. Methods-Prospective clinical information was collected for all patients adm itted with acute ischemic stroke between July 1995 and July 1996. A subgrou p of these patients was enrolled in a clinical trial of acute stroke therap y and had been randomly assigned to the placebo group. The control group wa s selected from concurrent stroke patients who were not enrolled in any cli nical trial. The National Institutes of Health Stroke Scale (NIHSS) was per formed on admission and on day 7 after admission. The Glasgow Outcome Scale (GOS) was also performed at discharge. Stroke severity was classified as " severe" if NIHSS was greater than or equal to 9 or GOS greater than or equa l to 3. Group comparisons were performed with chi(2) tests. Results-One hundred twenty-six patients were evaluated. Forty-seven were pl acebo patients, and 79 were selected as control subjects. There were no sig nificant differences between the groups with respect to age, sex, hematocri t, blood glucose level, history of hypertension, diabetes, smoking, or init ial NIHSS. In addition, there was no difference between groups in terms of the frequency of baseline stroke subtype, Among our controls, 55 patients ( 70%) were on antithrombotic treatment during hospitalization, whereas none of our placebo patients were on any antithrombotic treatment. For the GOS a t follow-up, a good outcome was attained by 76% of the control subjects and 72% of placebo patients (not significant). A severe NIHSS (>9) at follow-u p, however, was documented in 15% of controls and 59% of placebo patients ( P<0.001). There was a trend toward a higher ("worse") mean follow-up NIHSS among placebo patients (mean NIHSS, 11) versus controls (mean NIHSS, 6) (P = 0.09). Conclusions-Patients enrolled in the placebo arms of some acute clinical st roke trials have similar functional outcomes but more severe neurological d eficits at 1 week than did a control group. These findings might be partial ly explained by the withholding of antithrombotic medication and the exclus ion criteria inherent in most trials. Vigilance is required to ensure that all patients participating in stroke studies be guaranteed optimal known me dical therapy.