PATCH

 

PATCH

Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial

Baharoglu. Lancet 2016; 387:2605–2613. doi:10.1016/S0140-6736(16)30392-0

Clinical Question

  • In patients with acute intracerebral haemorrhage (ICH), associated with antiplatelet therapy, does platelet transfusion compared with standard care reduce death or dependence?

Design

  • Randomised controlled trial
    • Web-based randomisation system
    • Biased coin randomisation
  • Clinicians and patients non-blinded
  • Primary outcome assessed by blinded neurologist or research nurse performing either structured telephone interview or face to face consultation
  • Primary outcome modified from that specified in trial protocol. Modification occurred prior to unmasking the trial database and without knowledge of outcome data.
  • Intention to treat analysis
  • 91% power to detect a common odds ratio (OR) of 0.43 in an ordinal logistic regression analysis for all pairs of modified Rankin Scores (mRS) categories

Setting

  • 41 Hospitals in Europe (Netherlands, UK, France)
  • Feb 2009 – Oct 2015

Population

  • Inclusion criteria:
    • Adult patients
    • Non-traumatic supratentorial intracerebral haemorrrhage confirmed with brain imaging
    • GCS 8-15
    • Platelet transfusion could be initiated within 6 hours of symptom onset and within 90 minutes of brain imaging
    • Had been taking antiplatelet therapy for at least 7 days prior to ICH (COX inhibitor: aspirin carbasalate calcium, ADP receptor inhibitor: clopidogrel, adenosine re-uptake inhibitor: dipyridamole)
    • Baseline modified Rankin score of 0 (no symptoms) or 1 (no significant disability)
  • Exclusion criteria:
    • Blood on brain imaging suggestive of epidural or subdural haematoma
    • Underlying aneurysm or AV malformation
    • Planned surgical evacuation of ICH within 24 hours of admission
    • Intraventricular blood more than sedimentation in the posterior horns of the lateral ventricles
    • Previous adverse reaction to platelet transfusions
    • Known use of Vitamin K antagonist, unless INR ≤1.3
    • History of coagulopathy or platelet <100
    • Death appeared imminent
  • 190 patients randomised

Comparing baseline characteristics of intervention vs. control groups

  • Antiplatelet therapy pre-ICH
    • COX inhibitor alone: 73% vs. 84%
    • COX inhibitor + dipyridamole: 19% vs. 14%
  • Median GCS score: 14 vs. 15
  • Age >80: 29% vs. 37%
  • ICH volume >30ml: 34% v. 21%
  • Intraventicular extension: 13% vs 22%
  • Had exclusions to trial entry: 15% vs. 23%
    • Intraventricular haemorrhage: 12 patients vs. 20 patients
    • Infratentorial location of haematoma: 2 patients vs. 0 patients
    • Not taking antiplatelets: 1 patient vs 0 patient
    • Thrombocytopenia: 0 patient vs. 1 patient

Intervention

  • Platelet transfusion (leucocyte depleted)
    • 5 units if on COX inhibitor, 10 units if on ADP receptor inhibitor
    • n=97, of whom 4 did not receive platelet transfusion

Control

  • Standard care (not defined)
    • n=93, of whom 2 received platelet transfusion

Outcome

  • Primary outcome: difference in functional outcome at 3 months as assessed by mRS
    • Odds of a shift towards death or dependence at 3 months significantly higher in the intervention group than in standard care
      • Unadjusted OR 1.84, 95% C.I. 1.1-3.08, p=0.02
      • Adjusted OR 2.05, 95% C.I. 1.18-3.56, p=0.01
  • Secondary outcomes: Comparing intervention vs. control groups
    • Alive at 3 months: 68% vs. 77%, OR 0.62 (0.33-1.19), p=0.15
    • mRS score 4-6 at 3 months: 72% vs 56%, OR 2.04 (1.12-3.74), p=0.02, fragility index 2 patients, with number of patients lost to follow up of 0 patients
    • mRS score 3-6 at 3 months: 89% vs 82%, OR 1.75 (0.77-3.97), p=0.18
    • Median ICH growth at 24 hr (ml) 2.01 vs. 1.16 , p=0.81, however baseline imaging values missing in 7 patients, and repeat imaging values missing in 37 patients
    • No significant difference in any serious adverse event
      • Overall: 42% vs. 29%, OR 1.79 (95% C.I. 0.98-3.27)
      • Thromboembolism: 4% vs. 1% OR 3.96 (95% C.I. 0.43-36.08)
      • Complication of ICH: 25% vs. 14% (OR 2.02 (95% C.I. 0.96-4.27)
  • Pre-specified sub-group
    • Haematoma volume
      • <7ml: OR 2.46 (95% C.I 1.02-5.94)
      • 7-30ml: OR 1.4 (95% C.I 0.58-3.39)
      • >30ml: 0.87 (95% C.I. 0.27-2.76)
      • (Odds ratio of >1 favours control group, where as OR <1 favours transfusion)
  • Post-hoc analysis
    • Primary outcome remained unchanged when the 36 patients who met at least 1 exclusion criteria were removed from analysis: adjusted OR 2.22 (95% C.I. 1.2-4.09), p=0.01

patch-data-table

patch-primary-outcome-chart

Authors’ Conclusions

  • Platelet transfusions cannot be recommended for the treatment of acute ICH in people taking antiplatelets therapy

Strengths

  • Randomised controlled trial
  • No patients lost to follow up at 3 months
  • blinding of assessors of primary outcome
  • Randomised control trial with allocation concealment maintained through web based randomisation

Weaknesses

  • Primary outcome changed during trial from dicotomised mRS to current one. However, this was changed prior to knowledge of the outcome data
  • Differences in the baseline characteristics between the intervention and the control group
  • Large numbers of patients randomised who had exclusion criteria
  • Non-blinding of clinicians and patients
  • Small numbers of patients included

The Bottom Line

  • This small randomised controlled trial demonstrated that patients with ICH who are on antiplatelet agents have worse neurological outcomes at 3 months if they are treated with a platelet transfusion compared with standard care alone. The trial has a number of weaknesses but this is the best evidence we have and I do not think we should be using platelet transfusions for these patients outside of a clinical trial.

External Links

Metadata

Summary author: @davidslessor
Summary date: 21st June 2016
Peer-review editor: @duncanchambler

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