STICH-II

Clinical Context

The original STICH trial, while not showing an overall benefit for early surgery in spontaneous supratentorial intracerebral hemorrhage (ICH), had pre-specified subgroup analyses that hinted at a potential benefit for patients with more superficial (lobar) hematomas, particularly if surgery was performed very early. This observation provided the rationale for STICH-II, which aimed to definitively test the hypothesis that early surgical evacuation via craniotomy would improve outcomes specifically in this subgroup of patients with lobar ICH who were conscious.

The management of lobar ICH often presents a clinical dilemma. These hematomas are surgically more accessible than deep ones, but patients are often less neurologically impaired at presentation, making the risk-benefit calculation for invasive surgery crucial. STICH-II sought to provide high-quality evidence to guide this decision-making process.

Patient Population

STICH-II enrolled 601 adult patients (≥18 years) from 78 centers in 26 countries. The key inclusion criteria targeted patients with:

• Spontaneous lobar ICH confirmed by CT, with the hematoma located within 1 cm of the cortical surface.
• Hematoma volume between 10 mL and 100 mL.
• A conscious state, defined by the best motor component of the Glasgow Coma Scale (GCS) being 5 or 6, AND the best verbal component being at least 1 (i.e., GCS ≥6 if intubated [suffix ‘T’], or GCS ≥7 if not intubated).
• Ability to undergo surgery within 48 hours of symptom onset (ictus), with an emphasis on performing surgery as early as possible (ideally within 12 hours).
• Clinical equipoise from the responsible neurosurgeon regarding the benefit of early surgery.

Exclusions included patients with deep hematomas (basal ganglia, thalamic), infratentorial hemorrhages, predominant intraventricular hemorrhage, or ICH secondary to known causes like tumors or vascular malformations.

The median age of participants was 65 years. About 60% were male. At randomization, patients were generally in good neurological condition: the median GCS was 13. The median hematoma volume was 36 mL.

Study Design

STICH-II was an international, multicenter, parallel-group randomized controlled trial.

Protocol Details

Eligible patients were randomized 1:1 to:

• Early Surgery Group: Intended surgical evacuation of the hematoma by craniotomy within 48 hours of ictus (ideally within 12 hours), plus best medical treatment.
• Initial Conservative Treatment Group: Best initial medical treatment according to local neurosurgical unit protocols. Surgery was reserved for patients who experienced subsequent neurological deterioration that was deemed to require surgical intervention.

Best medical treatment was not standardized but generally included intensive care unit or stroke unit admission, blood pressure management, and other supportive measures.

Outcome Assessment

The primary outcome was assessed at 6 months using the Extended Glasgow Outcome Scale (GOS-E), typically via postal questionnaire or telephone interview, with efforts to blind assessors to treatment allocation where feasible.

Power Analysis

The trial was designed to detect an absolute difference of 12% in unfavorable outcomes (death or severe disability) between the groups, assuming an unfavorable outcome rate of 45% in the conservative group and 33% in the surgery group, with 80% power at a 5% significance level, requiring approximately 600 patients.

Risk of Bias Analysis

(Content for this section needs to be added. Considerations: open-label nature of surgery, potential for performance bias, blinding of outcome assessment where possible.)

Results

A total of 601 patients were randomized: 307 to early surgery and 294 to initial conservative treatment. In the early surgery group, 91% received surgery, with a median time from ictus to surgery of 21 hours. In the initial conservative treatment group, 16% (47 patients) eventually underwent surgical hematoma evacuation due to neurological deterioration.

Primary Outcome: Unfavorable Outcome (Death or Severe Disability) at 6 Months

An unfavorable outcome (GOS-E categories: Dead, Vegetative State, or Severe Disability) at 6 months occurred in:

• 37% of patients in the early surgery group (110 of 295 evaluable patients)
• 38% of patients in the initial conservative treatment group (110 of 289 evaluable patients)

This difference was not statistically significant (odds ratio for an unfavorable outcome with early surgery, 0.96; 95% CI 0.70–1.32; p=0.806).

Secondary Outcomes

• Mortality at 6 months: 18% in the early surgery group versus 20% in the initial conservative treatment group (OR 0.88, 95% CI 0.58–1.34; p=0.552).
• Survival: No significant difference.
• Rankin Scale scores at 6 months: No significant difference between groups when analyzed ordinally or dichotomized.
• EuroQol (EQ-5D) quality of life: No significant difference.

Subgroup Analyses

No pre-specified subgroups showed a statistically significant benefit from early surgery, including analyses based on age, GCS, hematoma volume, or time to surgery.

Final Thoughts & Critical Appraisal

STICH-II was designed to test a promising hypothesis derived from subgroup analyses of the original STICH trial: that early surgery might benefit conscious patients with superficial lobar ICH. However, the results of this well-conducted trial did not confirm this hypothesis.

Key takeaways:

• No Overall Benefit for Early Surgery in Lobar ICH (Conscious Patients): For the specific population studied (conscious patients with lobar ICH 10-100 mL), a policy of early surgical evacuation via craniotomy did not improve the rate of favorable outcomes (survival without severe disability) or reduce mortality at 6 months compared to initial conservative management.
• Reinforces Selective Approach: STICH-II, like its predecessor, supports a more selective approach to surgery in ICH. It suggests that routine early craniotomy is not indicated for all patients with lobar ICH who are initially conscious.
• Importance of Specific Populations: This trial highlights that findings from one subgroup (even if pre-specified for exploration) in a larger trial need to be prospectively tested in a trial specifically designed for that population before being adopted into practice.
• Minimally Invasive Techniques?: STICH-II focused on craniotomy. It did not address the potential role of minimally invasive surgical techniques (e.g., stereotactic aspiration, endoscopic evacuation) for lobar ICH, which other trials (like MISTIE or ENRICH) have explored.

The findings of STICH-II were important in further refining the indications for surgical intervention in ICH and emphasized that even for surgically accessible hematomas in relatively good-grade patients, the benefits of early, conventional open surgery are not guaranteed and may not outweigh the risks or the outcomes achievable with modern medical management.

How do we reconcile the results with other studies?

(Content for this section needs to be added, discussing how STICH-II relates to STICH, MISTIE, ENRICH, and the evolving understanding of surgical roles in different ICH subtypes and with different techniques.)

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