Early 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

• [article] Early Surgery versus Initial Conservative Treatment in Patients with Traumatic Intracerebral Hemorrhage (STITCH[Trauma]): The First Randomized Trial
• [commentary]  Traumatic Intracerebral Haemorrhage and Recruitment.
• [commentary] JC: A Stitch in Time
• [commentary] LITFL Research and Reviews in the Fastlane 089

Metadata

Summary author: @dramstewart

Summary date: 3 February 2016

Peer-review editor: @DuncanChambler