PROACT II Study: A randomized controlled trial

Furlan A et al. Intra-arterial prourokinase for acute ischemic stroke JAMA 1999 282:21 2003-2011 "Prolyse in Cerebral thromboembolism 2" 180 patients with CVA< 6 hours with angiographically proven MCA occlusion without hemorrhage or early infarct signs at 54 sites. They were randomized to 9 mg IA pro UK plus heparin or just heparin. Main outcome measure was number with no disability ie modified Rankin of 2 or less at 90 days. Secondary outcomes were MCA recanalization, frequency of ICH, and mortality. 40 % of pro UK patients and 25 % controls had modified Rankin of 2 or less ( p=0.04). Mortality was 25 and 27 % respectively. Recanalization rate was 66 % and 18 % respeectively (p<0.001). SICH within 24 hours was 10 % and 2 % respectively. Conclusion- treatment improves outcome, main outcome measure.

Notes: angiographic inclusion criteria were TIMI grade 0 or 1 (no or minimal contrast perfusion). Randomization was 2:1, stratified into NIHSS 4-10, 11-20, and 21-30. ITT analysis was used. 12,323 patients were screened, 4 % (474) received angiography, of whom 180 were eligible and were randomized. Median NIHSS score was 18. The median time to initiation of treatment was 5.3 hours. 35 % v. 13 % suffered ICH (38/108' 7/54) although most were asymptomatic. SICH occurred in 10 % (11/108) v. 2 % (1/54) for a NTT to harm = 12. Compared to PROACT 1 which used smaller dose of pro-UK (6 v. 9) recanalization increased by 26 % but SICH increased by 4 %. The total ICH rates were similar to those reported in cases of embolic stroke. Higher rate of hemorrhage compared to iv tPA in NINDS (6.4%) ATLANTIS (7.2%) and ECASS II (8.8%) reflects baseline greater stroke severity and time to treatment in PROACT 2. Median NIHSS score was 17 in PROACT 2, 11 in ECASS 2 and AtTLANTIS, and 14 in NINDS. Recanalization rate of large vessel occlusion with iv tPA is 30 % (TIATTS study). Tomsick-- hyperdense MCA sign or NIHSS score > 10 predicts poor response to iv therapy. In this study only 1 patient was treated within 3 hours.