Combined Ruyi Zhenbao Pills-Baimai Ointment Therapy on Acute Ischemic Stroke: A Multi-Arm, Randomized, Double-Blind, Placebo Controlled Clinical Study.

The short version

This multicenter, double-blind trial of 423 adults analyzed tested two Tibetan medicine products, Ruyi Zhenbao Pills taken by mouth and Baimai Ointment rubbed onto the weakened arm or leg, in acute ischemic stroke (a stroke caused by a blocked brain artery). Clot-removing treatments can only be used in a narrow time window, and neuroprotective drugs have not shown reliable benefit, so the investigators looked at formulations that had protected brain tissue in animal and cell studies. In Tibetan medical theory, the authors explain, stroke is a "white-meridian disease" involving disordered rlung (vital wind) and blood stasis, and pills and ointment are often used together. Participants were aged 18 to 75, within 14 days of a stroke presumed to come from narrowed large arteries, and were enrolled at 21 hospitals in China. They were randomly assigned to pills plus ointment, pills plus placebo ointment, ointment plus placebo pills, or two placebos, on top of standard stroke care. Treatment was twice daily for 8 weeks. Motor recovery was scored on the Fugl-Meyer assessment, a standard measure of arm and leg movement, and followed to day 90. By day 90, Fugl-Meyer scores had risen by 31.22 points with the combination, 29.25 with ointment alone and 29.88 with pills alone, compared with 19.20 with placebo (differences of 12.02, 10.05 and 10.68 points; all P < 0.001, roughly 50-60% larger gains than placebo). Independence in daily life (a modified Rankin score of 2 or less) was reached by 90-96% of treated participants versus 69.5% on placebo, and 64% to 73% reached a Barthel index of 95 or more (a near-complete self-care score) versus 45.7%. The three active groups did not differ from one another. Neurological deficit scores (NIHSS) at day 28 did not differ from placebo. Adverse events were similar across groups, with one serious event in each, and recurrent stroke or cerebrovascular events were rare (one per group). The authors report that both products improved motor recovery with acceptable safety. They also state that the trial included mostly mild strokes, that blood-pressure history was unevenly spread across groups, that the active ingredients are unknown, that the lack of difference between single products and the combination may reflect limited sample size, and that it covered only Chinese patients with one stroke type who had not received endovascular treatment.

Key findings

• In a double-blind trial of 423 adults within 14 days of an ischemic stroke (a stroke from a blocked brain artery), Tibetan Ruyi Zhenbao Pills, Baimai Ointment, or both, added to standard care, improved arm and leg movement scores (Fugl-Meyer assessment) by 29 to 31 points at day 90, compared with 19.20 points on placebo (all P < 0.001).
• Many more treated participants reached independence in daily life at day 90 (a modified Rankin score of 2 or less: 90-96% vs 69.5%) and a Barthel index of 95 or more (a near-complete self-care score: 64-73% vs 45.7%).
• The pills alone, ointment alone and the combination did not differ from each other, and the change in NIHSS (a stroke severity scale) at day 28 did not differ from placebo; adverse events were similar across groups, with one serious event in each.
• The strokes were mostly mild, all participants were Chinese with one stroke type, the active ingredients were not identified and hypertension was unevenly spread between groups, so the results are early evidence rather than proof for other populations.

Common questions