DESTINY
Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY): A Randomized, Controlled Trial
Clinical Question
Does decompressive hemicraniectomy reduce mortality and improve functional outcome compared to conservative treatment alone in patients aged 18-60 years with malignant middle cerebral artery infarction?
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
Design
Study Type: Prospective, multicenter, randomized, controlled, open-label trial with sequential design
Randomization: 1
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
Enrollment Period: February 2004 to October 2005
Follow-up Duration: 12 months
Centers: 6
Countries: Germany
Sample Size: 32
Analysis: Intention-to-treat and per-protocol. Sequential design using PEST 2.2 software. Chi-square test for primary endpoint. Wilcoxon U test for mRS distribution. Level of significance 5%, power 90%.
Inclusion Criteria
- Age 18-60 years
- Clinical signs of infarction of the MCA territory with NIHSS score ≥18 for nondominant hemisphere or ≥20 for dominant hemisphere
- Decrease in level of consciousness to score ≥1 on item 1a of NIHSS
- CT-documented unilateral MCA infarction including at least 2/3 of territory and at least part of basal ganglia, with or without additional ipsilateral ACA or PCA infarction
- Onset of symptoms >12 and <36 hours before possible surgical intervention
- Possibility to start treatment/surgery within 6 hours after randomization
- Written informed consent by patient or legal representative
Exclusion Criteria
- Pre-stroke mRS score ≥2
- Pre-stroke Barthel Index score <95
- Glasgow Coma Scale score <6
- Both pupils fixed and dilated
- Any other coincidental brain lesion that might affect outcome
- Space-occupying hemorrhagic transformation of the infarct
- Life expectancy <3 years
- Other serious illness that might affect outcome
- Known coagulopathy or systemic bleeding disorder
- Contraindication for anesthesia
- Pregnancy
Arms
| Field | Hemicraniectomy plus conservative treatment | Control |
|---|---|---|
| Intervention | Large (reversed) question mark-shaped skin incision. Removal of bone flap diameter >12 cm including frontal, parietal, temporal, and parts of occipital squama. Removal of additional temporal bone to explore floor of middle cerebral fossa. Dura opened with augmented dural patch (homologous periost and/or temporal fascia). No resection of infarcted brain tissue. ICP sensor inserted. Cranioplasty in survivors after 6-8 weeks. Plus standardized conservative treatment protocol. | Standardized protocol including: osmotherapy (mannitol, glycerol, or hydroxyethyl starch) for cerebral edema; intubation and mechanical ventilation if GCS <8; hyperventilation as ultima ratio; ICP monitoring in ipsilateral hemisphere; sedation (propofol recommended, barbiturates discouraged); blood pressure management; normothermia; blood glucose 80-110 mg/dL; normovolemia; DVT prophylaxis with LMWH; no seizure prophylaxis |
| Duration | Single surgical intervention with ongoing conservative care | Throughout ICU stay |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Functional outcome at 6 months measured by mRS, dichotomized to 0-3 (favorable) versus 4-6 (unfavorable) | Primary | 4/15 (27%) | 8/17 (47%) | 2.44 | 0.23 |
| 30-day mortality (first endpoint) | Secondary | 8/15 (53%) dead | 2/17 (12%) dead | Median unbiased OR 6.37 | 0.02 |
| Survival at 6 and 12 months | Secondary | 7/15 (47%) | 14/17 (82%) | OR 5.33 | 0.03 |
| mRS 0-4 at 6 months | Secondary | 5/15 (33%) | 13/17 (77%) | OR 6.50 | 0.01 |
| mRS distribution at 6 months (Wilcoxon U test) | Secondary | Median 6 (range 3-6) | Median 4 (range 2-6) | 0.04 | |
| mRS 0-3 at 12 months | Secondary | 4/15 (27%) | 8/17 (47%) | OR 2.44 | 0.23 |
| mRS 0-4 at 12 months | Secondary | 5/15 (33%) | 13/17 (77%) | OR 6.50 | 0.01 |
| mRS distribution at 12 months | Secondary | Median 6 (range 2-6) | Median 4 (range 2-6) | 0.04 | |
| Barthel Index at 6 months | Secondary | Median 0 (range 0-85) | Median 50 (range 0-85) | Median difference 20 | 0.08 |
| Barthel Index at 12 months | Secondary | Median 0 (range 0-95) | Median 45 (range 0-95) | Median difference 25 | 0.07 |
| NIHSS at 6 months | Secondary | Median 42 (range 12-42) | Median 14 (range 10-19) | Median difference -7 | 0.04 |
| NIHSS at 12 months | Secondary | Median 42 (range 6-42) | Median 13 (range 5-42) | Median difference -7 | 0.05 |
| Patient/caregiver agreement with procedure at 12 months | Secondary | N/A | 100% | ||
| Death within 8 days | Adverse | 7/15 (47%) | 1/17 (6%) | ||
| Late death (after 8 days) | Adverse | 1/15 (7%) | 1/17 (6%) - fatal PE day 157 post-cranioplasty | ||
| mRS 5 among survivors at 6 months | Adverse | 2/7 (28%) | 1/14 (7%) |
Subgroup Analysis
Higher proportion of dominant hemisphere infarctions in conservative treatment arm (73% vs 53%, p=0.23, not significant). Higher median NIHSS in conservative arm (24 vs 21, p<0.01). No formal subgroup analyses reported.
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
Funding
Not explicitly stated in the paper
Based on: DESTINY (Stroke, 2007)
Authors: Eric Jüttler, Stefan Schwab, Peter Schmiedek, ..., for the DESTINY Study Group
Citation: Stroke. 2007;38:2518-2525
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