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evident
Original paper
1999JAMANeurology

PROACT II

Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study

RCTAcute ischemic stroke

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Overview

Intra-arterial prourokinase improved outcomes in MCA stroke but increased symptomatic ICH.

Clinical takeaway

PROACT II is a historical bridge between IV thrombolysis and modern endovascular stroke therapy, showing the promise and bleeding risk of intra-arterial reperfusion.

Key result

Modified Rankin Scale 0-2 at 90 days was 40% with intra-arterial prourokinase vs 25% with heparin alone (P=0.04).

Practice impact

Helped establish endovascular reperfusion as biologically plausible before modern thrombectomy trials.

Evidence

Study design

Randomized, controlled, multicenter, open-label trial with blinded follow-up.

Enrollment

180

Follow-up

90 days.

Geography

United States, Canada

Clinical question

Does intra-arterial recombinant prourokinase improve outcomes in acute MCA occlusion treated within 6 hours?

Population

  • Patients with acute ischemic stroke due to middle cerebral artery occlusion within 6 hours of symptom onset.

Intervention

Intra-arterial recombinant prourokinase 9 mg plus heparin.

Comparator

Heparin alone.

Primary outcome

Modified Rankin Scale 0-2 at 90 days.

Intra-arterial prourokinase increased functional independence after acute MCA occlusion (40% vs 25% mRS 0-2; P=0.04) but increased symptomatic hemorrhage.

Absolute rates / p=0.04

Key results

  • Modified Rankin Scale 0-2 at 90 days: 40% with prourokinase vs 25% with heparin alone (P=0.04).
  • MCA recanalization: 66% with prourokinase vs 18% (P<0.001).
  • Intracranial hemorrhage with neurological deterioration within 24 hours: 10% vs 2% (P=0.06).
  • Mortality was similar: 25% vs 27%.

Harms

  • Symptomatic intracranial hemorrhage was increased.
  • Intra-arterial thrombolysis has largely been superseded by mechanical thrombectomy for eligible large-vessel occlusion.

Clinical Use

Practice impact

  • Historical landmark for intra-arterial reperfusion and the evolution toward thrombectomy.

Applicability

  • Primarily historical; modern practice relies on IV thrombolysis and mechanical thrombectomy selection.

Limitations

  • Small trial using an agent and approach not central to current practice.
  • Superseded by stent-retriever thrombectomy trials such as MR CLEAN.

Common misinterpretations

  • Do not use PROACT II to choose intra-arterial lytics over modern thrombectomy when thrombectomy is available.

Related evidence

NINDS tPA - ContextMR CLEAN - Superseded By

Citation

Furlan A, Higashida R, Wechsler L, et al. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. JAMA. 1999;282(21):2003-2011. doi:10.1001/jama.282.21.2003

For the primary analysis, 40% of r-proUK patients and 25% of control patients had a modified Rankin score of 2 or less (P = .04).