IV Recombinant human prourokitrialas effective as Alteplase in Acute Ischemic Stroke: JAMA
Phase 3 results of the PROST trial revealed that intravenous therapy of Recombinant human prourokinase (rhPro-UK), when administered within 4.5 hours of acute ischemic stroke, was safe, effective, reduced systemic bleeding risk, and was as effective as Alteplase. The rate of symptomatic intracranial hemorrhage was similar between the two groups.
The results of this phase 3 trial were published in the journal JAMA Network Open on July 25th, 2023.
Patients with acute ischemic stroke (AIS) should receive intravenous thrombolysis (IVT) within 4.5 hours of the start of symptoms. Alteplase is the recombinant tissue plasminogen activator, an optimum thrombolytic drug being administered. Recombinant human prourokinase (rhPro-UK) with a sequence identical to that of natural prourokinase is efficacious in treating acute myocardial infarction (AMI). Researchers from China successfully conducted a phase 2 trial of rhPro-UK administration within 4.5 hours of AIS onset. Hence the researchers extended to the phase 3 trial to evaluate the efficacy and safety of rhPro-UK thrombolysis within 4.5 hours of symptom onset in patients with AIS between May 2018 to May 2020 at various centers in China.
PROST trial was a randomized, alteplase-controlled, open-label, phase 3 clinical trial. After screening nearly 684 patients, the researchers enrolled 674 patients aged 18 to 80 years with a diagnosis of AIS and received treatment within 4.5 hours of stroke onset. All the eligible patients were randomly assigned (1:1) to receive intravenous rhPro-UK or Alteplase. The primary objective was to assess the noninferiority of rhPro-UK to alteplase. The noninferiority margin was a between-group difference of less than 10%. The primary outcome was a modified Rankin Scale score of 0 to 1 at 90 days.
Key findings:
- Among 663 patients in the modified intention-to-treat population with a mean age of 61 years, there were 161 females [24.3%].
- After randomization, there were 330 patients in the rhPro-UK group and 333 patients in the alteplase group.
- The median (IQR) baseline National Institutes of Health Stroke Scale score was 6.00 (5.00-9.00).
- There were 23 deaths, and 619 patients (93.4%) completed the 3-month follow-up.
- The primary outcome occurred in 215 patients (65.2%) in the rhPro-UK group and 214 patients (64.3%) in the alteplase group.
- Symptomatic intracerebral hemorrhage occurred in 5 patients (1.5%) in the rhPro-UK group and 6 patients (1.8%) in the alteplase group (P > .99).
- Systemic bleeding within 90 days occurred more frequently in the alteplase group (141 patients ) than in the rhPro-UK group (85 patients) (P < .001).
- By 90 days, 5 thrombolysis-related deaths each had occurred in the rhPro-UK group (1.5%) and alteplase group (1.5%) (P > .99).
Thus, the prospective evidence from this large-scale multicentre trial showed that rhPro-UK was safe, effective, and non-inferior to alteplase.
Further reading: Song H, Wang Y, Ma Q, et al. Efficacy and Safety of Recombinant Human Prourokinase in the Treatment of Acute Ischemic Stroke Within 4.5 Hours of Stroke Onset: A Phase 3 Randomized Clinical Trial. JAMA Netw Open. 2023;6(7):e2325415. doi:10.1001/jamanetworkopen.2023.25415
