DESTINY
Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY): A Randomized, Controlled Trial
Year of Publication: 2007
Authors: Eric Jüttler, Stefan Schwab, Peter Schmiedek, ..., for the DESTINY Study Group
Journal: Stroke
Citation: Stroke. 2007;38:2518-2525
Link: https://doi.org/10.1161/strokeaha.107.485649
PDF: https://www.ahajournals.org/doi/pdf/10.1...EAHA.107.485649
PDF: 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?
Study Overview
Objective
To evaluate whether decompressive hemicraniectomy reduces mortality and improves functional outcome compared to conservative treatment in patients with malignant MCA infarction
Study Summary
- Hemicraniectomy significantly reduced 30-day mortality (12% vs 53%, p=0.02)
- 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
Patients per Arm
Surgery: 17; Conservative: 15
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
Baseline Characteristics
| Characteristic | Conservative | Surgery |
|---|---|---|
| N | 15 | 17 |
| Sex - Male | 47% | 47% |
| Sex - Female | 53% | 53% |
| Age - Mean ± SD | 46.1 ± 8.4 years | 43.2 ± 9.7 years |
| Age - Median | 46.0 years | 43.0 years |
| Age - Range | 29.0-59.0 years | 30.0-60.0 years |
| Hemisphere - Dominant | 73% | 53% |
| Hemisphere - Nondominant | 27% | 47% |
| NIHSS score on admission - Median | 24 | 21 |
| NIHSS score on admission - Range | 19-31 | 19-26 |
| Time from symptom onset to treatment - Mean ± SD | 23.8 ± 7.8 hours | 24.4 ± 6.9 hours |
| Time from symptom onset to treatment - Median | 22.5 hours | 24.0 hours |
| Time from symptom onset to treatment - Range | 12.0-35.0 hours | 13.5-36.0 hours |
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 survival (first endpoint) | Secondary | 7/15 (47%) alive | 15/17 (88%) alive | 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 | 8/15 (53%) | 2/17 (12%) | ||
| Late death (after 8 days) | Adverse | 0/15 (0%) | 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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