DESTINY: Decompressive Hemicraniectomy in Malignant MCA Infarction (2007)

“The results of our pooled analysis suggest that early decompressive hemicraniectomy increases the probability of survival in patients with malignant middle-cerebral-artery infarction.”

  • The DESTINY Study Group

1. Publication Details

  • Trial Title: Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY): a randomized, controlled trial
  • Citation: Jüttler E, Schwab S, Schmiedek P, et al. Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY): a randomized, controlled trial. Stroke. 2007;38(9):2518-2525. DOI: 10.1161/STROKEAHA.107.485649
  • Published: September 2007, in Stroke
  • Author: Eric Jüttler, M.D.
  • Funding: German Research Foundation.

2. Keywords

  • Ischemic Stroke, Malignant Middle Cerebral Artery Infarction, Decompressive Hemicraniectomy, Neurosurgery, Critical Care, Randomized Controlled Trial

3. The Clinical Question

  • In adult patients (18-60 years) with malignant middle cerebral artery (MCA) territory infarction (Population), does early decompressive hemicraniectomy (Intervention) compared to standard medical care (Comparison) reduce 30-day mortality (Outcome)?

4. Background and Rationale

  • Existing Knowledge: Malignant MCA infarction is a devastating form of ischemic stroke characterized by massive cerebral edema, leading to brain herniation and death in up to 80% of patients treated with medical therapy alone. Decompressive hemicraniectomy, a surgical procedure to remove a large part of the skull, was known to reduce intracranial pressure.
  • Knowledge Gap: While physiologically plausible, there was no high-quality evidence from randomized controlled trials to determine if this major surgical intervention improved survival in this patient population.
  • Proposed Hypothesis: The authors hypothesized that early decompressive hemicraniectomy (within 48 hours) would be superior to standard medical care in reducing mortality.

5. Study Design and Methods

  • Design: A multicenter, prospective, randomized, open-label, controlled trial (used to test the effectiveness of interventions).
  • Setting: 13 neurological and neurosurgical intensive care units (ICUs) in Germany.
  • Trial Period: Enrollment ran from March 2001 to April 2006.
  • Population:
    • Inclusion Criteria: Adult patients aged 18 to 60 years with clinical signs of a severe MCA stroke and a large infarct volume on CT/MRI, who could be randomized within 48 hours of symptom onset.
    • Exclusion Criteria: Included pre-existing severe disability (modified Rankin Scale score >2), bilateral fixed and dilated pupils, and severe comorbidities.
  • Intervention: Patients received a large decompressive hemicraniectomy (at least 12 cm in diameter) plus standard medical care.
  • Control: Patients received standard medical care alone, which included sedation, osmotherapy, and other measures to control intracranial pressure.
  • Management Common to Both Groups: All patients received best medical management for stroke according to guidelines at the time.
  • Power and Sample Size: The trial was part of a pre-planned pooled analysis with two other similar European trials (DECIMAL and HAMLET). The pooled analysis was designed to have sufficient power to detect a clinically meaningful difference in outcomes.
  • Outcomes:
    • Primary Outcome: All-cause mortality at 30 days.
    • Secondary Outcomes: Included functional outcome at 12 months, as measured by the modified Rankin Scale (mRS).

6. Key Results

  • Enrollment and Baseline: 32 patients were randomized in the DESTINY trial itself (17 to surgery and 15 to control). The groups were well-matched at baseline.
  • Trial Status: The trial was stopped early by the data and safety monitoring board after a pre-planned pooled analysis with the DECIMAL and HAMLET trials showed a clear and significant benefit for surgery.
  • Primary Outcome (Pooled Analysis): In the pooled analysis of all three trials (93 patients), 30-day mortality was dramatically lower in the hemicraniectomy group: 13 of 51 patients (25%) in the surgical group died, compared with 30 of 42 patients (71%) in the control group (p<0.0001).
  • Secondary Outcomes (Pooled Analysis): At 1 year, significantly more patients in the surgical group had a favorable functional outcome (mRS score ≤ 4), although a substantial proportion of survivors had moderate to severe disability.
  • Adverse Events: The study reported on complications related to the surgery, which were managed as expected.

7. Medical Statistics

  • Analysis Principle: The trial was analyzed using an intention-to-treat principle.
  • Statistical Tests Used: The primary outcome was analyzed using a chi-square test.
  • Primary Outcome Analysis: The primary outcome was a comparison of the proportions of death between the two groups in the pooled analysis.
  • Key Statistic(s) Reported: The key statistics were the absolute mortality rates and the associated P-value from the pooled analysis.
  • Interpretation of Key Statistic(s):
    • P-value: The p-value of <0.0001 for the primary outcome is extremely low, indicating a highly statistically significant result that is very unlikely to be due to chance (a result is conventionally considered statistically significant if the p-value is less than 0.05).
  • Clinical Impact Measures (Pooled Analysis):
    • Absolute Risk Reduction (ARR):
      • Formula: ARR = (Risk in Control Group) – (Risk in Intervention Group)
      • Calculation: ARR = 71% – 25% = 46%.
      • Clinical Meaning: For every 100 patients treated with hemicraniectomy, about 46 additional deaths were prevented at 30 days.
    • Number Needed to Treat (NNT):
      • Formula: NNT = 1 / ARR
      • Calculation: NNT = 1 / 0.46 = 2.2, which is rounded down to 2.
      • Clinical Meaning: You would only need to treat 2 patients with decompressive hemicraniectomy to prevent one additional death.
  • Subgroup Analyses: Not a major feature of this publication.

8. Strengths of the Study

  • Study Design and Conduct: The multicenter, randomized, controlled design, especially when combined in a pre-planned pooled analysis, provided high-quality evidence.
  • Generalizability: The inclusion of multiple centers increases the applicability of the findings.
  • Statistical Power: The pooled analysis was adequately powered and found a very large, significant effect.
  • Patient-Centered Outcomes: The study focused on the crucial outcomes of mortality and long-term functional status.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The study was open-label (unblinded), which is an unavoidable limitation for a major surgical trial.
  • External Validity (Generalizability): The trial had a strict upper age limit of 60 years. Therefore, the results cannot be directly generalized to older patients.
  • Other: The trial was stopped early for benefit, which can sometimes lead to an overestimation of the true treatment effect. The primary outcome was 30-day mortality, and while functional outcomes were assessed, the trial raises important ethical questions about saving patients to a state of severe disability.

10. Conclusion of the Authors

  • The authors concluded that in patients aged 18 to 60 with malignant MCA infarction, early decompressive hemicraniectomy is a life-saving procedure.

11. To Summarize

  • Impact on Current Practice: This trial, as part of the pooled European analysis, was profoundly practice-changing. It provided the first definitive evidence that decompressive hemicraniectomy saves lives in younger patients with malignant MCA stroke, establishing it as a standard of care.
  • Specific Recommendations:
    • Patient Selection: For adult patients aged 18-60 years with malignant MCA infarction.
    • Actionable Intervention: Proceed with emergent decompressive hemicraniectomy.
    • Expected Benefit: This intervention has a very large effect, with an NNT of only 2 to prevent one death.
  • What This Trial Does NOT Mean: This trial does NOT mean that all survivors will have a good functional outcome. A significant proportion of patients saved by the surgery are left with moderate to severe disability.
  • Implementation Caveats: This is a major neurosurgical procedure that requires a comprehensive stroke center with neurosurgical and neurocritical care expertise. The decision to proceed with surgery requires a careful discussion with the patient’s family about the high likelihood of survival with significant disability.

12. Context and Related Studies

  • Building on Previous Evidence: The DESTINY trial (2007), along with DECIMAL and HAMLET, was designed to provide high-quality RCT evidence for a practice that was based on physiological reasoning and case series.
  • Influence on Subsequent Research: The definitive positive result in younger patients led directly to the design of the DESTINY II trial (2014), which was specifically designed to test the same intervention in patients older than 60 years.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: The key unresolved question from this trial was whether the survival benefit of hemicraniectomy would extend to older patients (>60 years), who have a worse prognosis at baseline.
  • Future Directions: The DESTINY II trial was the direct successor to this study, designed to answer the question of efficacy in the elderly population.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The research question was highly relevant, addressing a devastating condition with extremely high mortality.
  • Methods: The multicenter RCT design and pre-planned pooled analysis were of high quality. The main methodological limitation is the open-label design, though this is unavoidable for this type of surgical intervention. The upper age limit of 60 is a key factor in interpreting the applicability of the results.
  • Results: The study reported a very large and statistically overwhelming benefit for the intervention, with an extremely low p-value and a very impressive NNT of 2. The trial was appropriately stopped early for efficacy.
  • Conclusions and Applicability: The authors’ conclusion is strongly supported by the data. The trial is a landmark in stroke care, establishing a life-saving surgical intervention. However, the applicability is strictly limited to the younger patient population studied, and the findings must be discussed with families in the context of the high rate of post-operative disability.

16. Disclaimer and Contact

  • This summary is provided by the Academic Committee of ESBICM (ACE) to facilitate the understanding of this study; readers are advised to refer to the original trial document for a deeper understanding. If you find any information incorrect, or missing, or it needs an update or have a request for a specific critical care trial summary, kindly write to us at academics[at]esbicm.org.
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