STITCH (trauma)

stitch(trauma) header imageEarly Surgery versus Initial Conservative Treatment in Patients with Traumatic Intracerebral Haemorrhage

Mendelow. Journal of Neurotrauma 2015;32(17):1312-1323. doi:10.1089/neu.2014.3644

Clinical Question

  • In patients with traumatic intracerebral haemorrhage (TICH), does early surgery (haematoma evacuation within 12 h of randomisation) compared with initial conservative management reduce major disability and death at 6 months after injury?

Design

  • International, multicentre, prospective, patient-randomised, parallel- group pragmatic trial
  • Centralised randomisation stratified by geographical region with minimisation procedure based on age group, and severity (measured by pupil equality and reactivity), with a random component (probability of 80%)
  • Appropriate concealment of allocation until randomisation
  • Open-label – patients, families and treating clinicians aware
  • Outcome assessed at 6 months by postal questionnaire or interview assessment (blinded)
  • Intention to treat analysis
  • Powered at 80% to detect a 10% absolute increase in the rate of favourable outcome from an expected incidence of 50% with conservative treatment and an alpha level of 0.05 if 840 patients were included
    • The funding agency decided to halt this study with effect from the end of September 2012 for “failure to recruit in the UK”
    • Modified protocol powered at 80% to detect a 21% absolute increase in the rate of favourable outcome from an average favourable outcome of 60%

Setting

  • 170 patients randomised from 31 of 59 registered centres in 13 countries worldwide
  • December 2009 to September 2012

Population

  • Inclusion: TICH patients for whom the treating neurosurgeon was in equipoise about the benefits of early surgical evacuation, compared with initial conservative treatment
    • Within 48 h of traumatic brain injury (TBI) and had evidence of a TICH on CT with a confluent volume of greater than 10mL (initially within 24h of TICH but subsequently increased)
  • Exclusion:
    • significant surface haematoma (extra-dural haemorrhage or subdural haemorrhage) requiring surgery
    • 3 or more separate haematomas
    • cerebellar haemorrhage/contusion
    • where surgery could not be performed within 12 h of randomisation
    • severe pre-existing physical or mental co-morbidity
    • permanent residence outside a study country
    • patient/relative preference for one treatment option
  • 1735 patients screened at sites completing logs, (111 were randomised from centres not completing logs)
  • Total of 170 randomised, 2 excluded due to different treatment decisions prior to randomisation, 1 lost to follow-up
  • 167 analysed in an intention-to-treat analysis (116 received intended treatment)

Intervention

  • Early evacuation of the haematoma by a method of the surgeon’s choice (within 12h of randomisation), combined with appropriate best medical treatment
    • 21 patients did not receive early surgery as assigned

Control

  • Initial conservative treatment was best medical treatment combined with delayed (more than 12 h after randomisation) evacuation if indicated by GCS, neurology and ICP/CPP (cerebral perfusion pressure) in invasively monitored patients
    • 31 patients did not receive conservative treatment as assigned

Management Common to Both Groups

  • Coagulopathies corrected prior to randomisation
  • Best medical treatment could include (depending on the practices within the centre) monitoring of ICP or other modalities and management of metabolism, sodium osmotic pressure, temperature, and blood gasses
  • All patients had a CT scan at 5 days (+/–2 days) after randomisation to assess changes in haematoma size

Outcome

  • Primary outcome: A non-significant benefit of early surgery on the dichotomised GOS favourable vs unfavourable outcome
      • Favourable = good recovery or moderately dependent
      • Unfavourable = severely dependent, vegetative, or dead
    • Unfavourable outcome in early surgery group 37% vs initial conservative management group 47% (OR, 0.65; 95% CI 0.35–1.21; p = 0.17)
    • Absolute difference of 10.5% (95% CI – 4.4–25.3)
    • Sensitivity analysis using logistic regression adjusting for age, volume, and GCS gives an OR of 0.58 (95% CI 0.29–1.16; p = 0.122)

  • Secondary outcome: Significant benefit of early surgery on 6-month mortality
    • 6-month mortality in early surgery group 15% vs initial conservative patients 33% (OR, 0.35; 95% CI 0.16–0.75; p = 0.007)
    • Absolute difference of 18.3% (95% CI 5.7–30.9)

Authors’ Conclusions

  • A larger trial is needed to confirm this potentially very beneficial effect of earlier surgery
  • In the interim, there is a strong case for operating on patients with TICH who have a GCS of 9–12
  • A strategy of early surgery is associated with a small, non-significant increase in health care costs

Strengths

  • Relevant clinical question
  • Randomised
  • Multi-centre
  • Outcome assessor blinded
  • Intention-to-treat analysis

Weaknesses

  • Internal Validity:
    • Initial trial protocol published a priori but subsequently modified due to premature termination of trial and decreased sample size
    • Temporal inclusion window from TBI increased from 24 h to 48 h during the trial to increase recruitment
    • Large number of crossovers with a long time window from TBI to randomisation and significant departures from intended treatment
    • Exploratory analyses of their effect on outcome and per treatment analyses currently unpublished
    • 111 patients recruited from centres where screening logs were not collated
    • Difficult to standardise clinical equipoise
    • Dichotomised GOS used instead of ordinal GOSE analysis in primary outcome measure
  • External Validity
    • ICP monitoring only undertaken in 24 (14%) patients
    • Underpowered study and only 4% of patients (6) recruited in the UK, most patients recruited from India and China with very different demographics and healthcare systems
    • Secondary outcome measure of mortality likely to be multifactorial in aetiology and not as clinically relevant as morbidity in the context of TBI
    • The secondary outcome analysis demonstrates a significant improvement in mortality offset by a non-significant increase in severely dependent patients
      • The health care costs associated with a potential increase in severely dependent patients is not factored into the costing analysis

The Bottom Line

  • Early surgery in TICH cannot be recommended solely on this evidence of a mortality benefit, a larger trial with a patient population generalisable to the UK is needed to explore if early surgery improves functional outcome in TICH

External Links

Metadata

Summary author: @dramstewart

Summary date: 3 February 2016

Peer-review editor: @DuncanChambler

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