DESTINY
(2007)Objective
To evaluate whether decompressive hemicraniectomy reduces mortality and improves functional outcome compared to conservative treatment in patients with malignant MCA infarction
Study Summary
• No significant difference in mRS 0-3 at 6 months (47% vs 27%, p=0.23), but significant shift in mRS distribution favoring surgery
• Trial stopped early; results contributed to pooled analysis showing clear benefit of decompressive surgery
Intervention
Decompressive hemicraniectomy (≥12 cm bone flap) plus conservative treatment vs conservative treatment alone
Inclusion Criteria
Age 18-60 years, MCA infarction ≥2/3 territory including basal ganglia, NIHSS ≥18 (non-dominant) or ≥20 (dominant), decreased consciousness, onset 12-36 hours before surgery, pre-stroke mRS ≤1
Study Design
Arms: Hemicraniectomy plus conservative treatment vs Conservative treatment alone
Patients per Arm: Surgery: 17; Conservative: 15
Outcome
• mRS 0-3 at 6 months: 47% vs 27% (p=0.23)
• mRS 0-4 at 6 months: 77% vs 33% (OR 6.50, p=0.01)
Bottom Line
Hemicraniectomy significantly reduces mortality in malignant MCA infarction (88% vs 47% survival at 30 days). While the primary endpoint of mRS 0-3 did not reach significance due to small sample size, there was a significant shift in mRS distribution favoring surgery, and importantly, severe disability (mRS 5) was not increased in survivors.
Major Points
- Trial stopped early after 32 patients when 30-day mortality endpoint reached statistical significance
- 30-day survival: 88% surgery vs 47% conservative (p=0.02, OR 6.37)
- 6- and 12-month survival: 82% surgery vs 47% conservative (p=0.03, OR 5.33)
- Primary endpoint mRS 0-3 at 6 months: 47% surgery vs 27% conservative (p=0.23, not significant)
- mRS 0-4 at 6 months: 77% surgery vs 33% conservative (p=0.01, OR 6.50)
- mRS distribution analysis showed significant benefit for surgery (p=0.04)
- Only 7% of surgical survivors had mRS 5 vs 28% of conservative survivors
- 100% of surgical survivors and caregivers agreed with the procedure at 12 months
- Part of pooled analysis with DECIMAL and HAMLET showing consistent benefit
Study Design
- Study Type
- Prospective, multicenter, randomized, controlled, open-label trial with sequential design
- Randomization
- Yes
- Blinding
- No blinding for treatment or outcome assessment. Single investigator conducted 6- and 12-month follow-ups who was not involved in screening, randomization, or patient care
- Sample Size
- 32
- Follow-up
- 12 months
- Centers
- 6
- Countries
- Germany
Primary Outcome
Definition: Functional outcome at 6 months measured by mRS, dichotomized to 0-3 (favorable) versus 4-6 (unfavorable)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 4/15 (27%) | 8/17 (47%) | 2.44 (0.55-10.83) | 0.23 |
Limitations & Criticisms
- Small sample size (n=32) - primary endpoint did not reach statistical significance
- 81% of patients from only 2 centers (Heidelberg and Mannheim) - essentially an oligocenter trial
- No blinding for treatment allocation or outcome assessment - potential bias
- Two major protocol violations (both patients survived)
- Imbalances at baseline: higher NIHSS and more dominant hemisphere infarctions in conservative arm
- Does not provide data on patients >60 years of age
- Projected sample size was 188 patients but trial stopped early
- Sequential design means multiple interim looks at the data
Citation
Stroke. 2007;38:2518-2525