Placebo treatment in acute stroke trials : benefit or harm to patients?

BACKGROUND AND PURPOSE Some stroke patients and their families express reservations about participating in trials of experimental therapies for acute stroke. Among many reasons given for this is the concern that by participating, patients may be deprived of some component of routine care. We sought to determine the effect on outcome of participating in a clinical stroke trial while being treated with placebo. METHODS Prospective clinical information was collected for all patients admitted with acute ischemic stroke between July 1995 and July 1996. A subgroup of these patients was enrolled in a clinical trial of acute stroke therapy and had been randomly assigned to the placebo group. The control group was selected from concurrent stroke patients who were not enrolled in any clinical trial. The National Institutes of Health Stroke Scale (NIHSS) was performed 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 >/=9 or GOS >/=3. Group comparisons were performed with chi(2) tests. RESULTS One hundred twenty-six patients were evaluated. Forty-seven were placebo patients, and 79 were selected as control subjects. There were no significant differences between the groups with respect to age, sex, hematocrit, blood glucose level, history of hypertension, diabetes, smoking, or initial 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 at 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-up, 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 stroke trials have similar functional outcomes but more severe neurological deficits at 1 week than did a control group. These findings might be partially explained by the withholding of antithrombotic medication and the exclusion criteria inherent in most trials. Vigilance is required to ensure that all patients participating in stroke studies be guaranteed optimal known medical therapy.