Factors Influencing Outcome and Treatment Effect in PROACT II
PROACT II was a randomized controlled trial of intra-arterial thrombolysis with recombinant prourokinase (r-proUK) plus low-dose heparin vs. low-dose heparin alone. In the primary outcome analysis, 40% of patients treated with r-proUK and 25% of control patients had a good neurological recovery at 90 days defined by a modified Rankin score≤2 (p=.043). Objective: To identify prognostic factors for the primary outcome measure and determine whether the treatment effect of r-proUK was consistent across subgroups stratified according to risk. Methods: Twenty-seven baseline categorical variables and 11 quantitative variables were selected. Stepwise logistic regression was used to identify important prognostic factors and to create a score which subdivided the study group into risk quartiles. Treatment effect was calculated as an odds ratio (OR) within each quartile and compared with a Breslow-Day test. Results: Three baseline variables were identified as strongly influencing the probability of a good outcome; Age ≤ 68 (p<0.0001, OR=4.3), CT hypodensity ≤ 5.25ml (p=0.038, OR=2.1), NIHSS score: (p= 0.0005, OR(11–20)=0.36, OR(>20)=0.085, relative to NIHSS≤10). The effect of treatment in the risk quartiles is summarized in the Table. Comparison of the size of the treatment effect over risk quartiles was non-significant p=0.91. Conclusion: Despite stratification of patients based on important prognostic variables there was no evidence of a difference in treatment effect across risk categories. All PROACT eligible patients stand to benefit from early intra-arterial r-proUK treatment.