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Keywords:

  • decompressive surgery;
  • elder stroke patients;
  • hemicraniectomy;
  • ischaemic stroke;
  • malignant MCA infarct;
  • randomised trial

Abstract

  1. Top of page
  2. Abstract
  3. Executive summary
  4. Introduction and rationale
  5. Methods
  6. Summary and conclusions
  7. References

Background Patients with severe space-occupying – so-called malignant – middle cerebral artery infarcts have a poor prognosis even under maximum intensive care treatment. Randomised trials demonstrated that early hemicraniectomy reduces mortality from about 70% to 20% without increasing the risk of being very severely disabled. Hemicraniectomy increases the chance to survive completely independent more than fivefold and doubles the chance to survive at least partly independent. Only patients up to 60-years have been included in these trials. However, patients older than 60-years represent about 50% of all patients with malignant middle cerebral artery infarcts. Data from observational studies, suggesting that older patients may not profit from hemicraniectomy, are inconclusive, because these patients have generally been treated later and less aggressively. This leads to great uncertainty in everyday clinical practice.

Aims To investigate the efficacy of early hemicraniectomy in patients older than 60-years with malignant MCA infarcts.

Materials & Methods DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY II is a randomised controlled trial including patients 61-years and older with malignant middle cerebral artery infarcts. Patients are randomised to either maximum conservative treatment alone or in addition to early hemicraniectomy within 48 h after symptom onset. The trial uses a sequential design with a maximum number of 160 patients to be enrolled (ISRCTN 21702227).

Discussion In the face of an ageing population, the potential benefit of hemicraniectomy in older patients is of major clinical relevance, but remains controversial.

Conclusion The results of this trial are expected to directly influence decision making in these patients.


Executive summary

  1. Top of page
  2. Abstract
  3. Executive summary
  4. Introduction and rationale
  5. Methods
  6. Summary and conclusions
  7. References

Rationale

About 50% of all patients with malignant middle cerebral artery (MCA) infarcts are older than 60-years. The benefit of hemicraniectomy in these patients is unclear. Data from observational studies are rare and inconclusive, because older patients in these studies were usually treated later and less aggressively than younger patients.

Aim and hypothesis

DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY II (DESTINY II) aims to investigate the benefit of early hemicraniectomy in addition to maximum conservative treatment to reduce death and very severe disability compared with maximum conservative treatment alone in patients with malignant MCA infarcts, who are older than 60-years. The primary aim is to assess whether decompressive surgery reduces mortality without increasing the number of very severely disabled – i.e. completely dependent and bedridden – survivors.

Design

DESTINY II is a prospective, randomised, controlled, open, multicentre, two-armed, comparative trial. Patients are randomised to either conservative treatment alone or hemicraniectomy plus conservative treatment within 48 h of symptom onset. The trial uses a sequential statistical design analysing statistical significance of the primary endpoint after every single patient having reached this endpoint. The trial will be stopped as soon as there is a statistically significant difference between the two treatment groups.

Study outcomes

The primary endpoint is the patient's disability after six-months measured by the modified Rankin Scale (mRS) and dichotomised 0–4 vs. 5 or 6. Secondary endpoints are assessed after one-year including global disability, activities of daily living, neurological deficit, speech and language disturbance, depression, quality of life, complications of operative treatment, and retrospective agreement to treatment.

Discussion

To clarify the potential benefit of hemicraniectomy in older patients with malignant MCA infarcts, a randomised trial is clearly needed. The results of this trial are expected to directly influence decision making in acute ischaemic stroke treatment in the future.

Introduction and rationale

  1. Top of page
  2. Abstract
  3. Executive summary
  4. Introduction and rationale
  5. Methods
  6. Summary and conclusions
  7. References

Space-occupying cerebral ischaemic infarcts are associated with cytotoxic, interstitial, and vasogenic brain oedema of different extents. Depending on the celerity and extent of oedema formation, and on individual compensating mechanisms of the patient, ischaemic brain oedema in large space-occupying MCA infarcts may lead to transtentorial or transforaminal herniation usually after two–five-days (1–3). Herniation is responsible for 78% of deaths during the first week (4). For these catastrophic infarcts, the term malignant MCA infarcts was introduced (2).

Conservative intensive care treatment strategies include osmotherapy with glycerol, mannitol, or hyperosmolar hydroxyl–ethyl starch, intracranial pressure (ICP)-lowering therapies with barbiturates, buffer solutions or hyperventilation, and neuroprotective therapies such as moderate hypothermia (5). None of these therapies are supported by adequate evidence from clinical trials (6, 7). Their benefit in malignant MCA infarction is doubtful and several authors argue that they are ineffective or even detrimental (5–8). In particular, ICP-lowering therapies guided by ICP monitoring seem to have little effect (9). This may be explained by the fact that displacement of brain tissue plays the pivotal role in these infarcts, whereas increased ICP usually occurs late, if it occurs at all (9, 10). Not surprisingly, this is reflected by clinical findings: prognosis of patients with malignant oedema formation after MCA infarct is poor despite maximum conservative treatment, and in randomised or larger prospective observational studies, mortality averages 50–80% (2, 11–16). Despite their doubtful benefit, conservative treatment options are currently used in many centres treating patients with ischaemic infarcts and space-occupying brain oedema (17).

In contrast to therapies targeting ICP, decompressive hemicraniectomy is based on mechanical thinking: temporary removal of a part of the skull would allow oedematous tissue to stretch outside the neurocranium, thereby avoiding fatal displacement of brain tissue. Lowering of ICP and consecutive restoration of cerebral perfusion are probably a secondary result (9). The procedure can be performed in every neurosurgical centre.

The benefit of hemicraniectomy in malignant MCA infarct has been demonstrated in three randomised trials and a pooled analysis (13–16): early hemicraniectomy reduces mortality from 71% to 22%. The proportion of patients who remain very severely disabled is small and is not increased by hemicraniectomy compared with conservative treatment (4% vs. 5%). Forty-three per cent of patients after hemicraniectomy show a good clinical outcome regarding the severity of these infarcts (mRS score 2–3), compared with 21·5% of those treated conservatively. The proportion of patients who are independent in their activities of daily living (mRS score 2) increases more than five times, from 2·5% to 14%. Likewise, however, the proportion of patients with moderate-to-severe disability (mRS score 4) increased more than 12-fold (31% vs. 2·5%) (13).

The upper age limit in the randomised trials was 60-years and left the question of a benefit of hemicraniectomy in older patients unresolved. According to the results of observational trials, mortality in older patients is not increased after conservative treatment and amounts 50–80% (2, 11, 12). Data on functional outcome in these patients, however, are insufficient. Larger case series on hemicraniectomy show more heterogeneous results: in a study by Uhl et al. (18), 12% of patients older than 50-years were independent, 37% died or were severely disabled. Gupta et al. (19) reported an independent outcome in only 1% of patients older than 50-years; 80% were severely disabled or died. None of these studies had a control group. In the largest prospective comparative study, mortality after conservative treatment in patients older than 60-years was 81% vs. 50% after hemicraniectomy. No patient was very severely disabled (mRS score 5) (20). However, of the 53 patients included in this study, only 17 were older than 60-years, and six of these were treated by hemicraniectomy.

None of the published studies including patients older than 60-years with malignant MCA infarcts was randomised, most were retrospective, and treatment procedures varied considerably. Most of all, possible prognostic factors such as occlusion of the internal carotid artery, additional infarcts of the anterior cerebral artery (ACA), and/or the posterior cerebral artery (PCA), stroke severity, and time to treatment differed between younger and older patients: older patients in these studies showed a trend towards more severe infarcts, but were treated less aggressively, especially when additional infarcts of the ACA or PCA were present or when they deteriorated early. In addition, hemicraniectomy in older patients was performed later and therapy was less often escalated and/or sooner ceased. Reasons for later intervention may be the belief that compared with younger patients older patients may less likely proceed to herniation due to more compensating intracranial space, i.e. lower average brain volumes and greater CSF space. Altogether, this may have resulted in a self-fulfilling prophecy with higher mortality rates of older patients in reported studies (21).

Methods

  1. Top of page
  2. Abstract
  3. Executive summary
  4. Introduction and rationale
  5. Methods
  6. Summary and conclusions
  7. References

Design

DESTINY II is a prospective, randomised, controlled, open, multicentre, two-armed, comparative trial (Fig. 1). Patients are randomised 1 : 1 to either conservative treatment alone or hemicraniectomy within 48 h of symptom onset plus conservative treatment. The trial uses a sequential statistical design analysing statistical significance of the primary endpoint after every single patient having reached this endpoint. The trial will be stopped as soon as there is a statistically significant difference between the two treatment groups.

image

Figure 1.  Study flow chart of the DESTINY II trial.

Download figure to PowerPoint

Based on the experience of DESTINY I, blinding is impossible for treating physicians and patients as well as for most of the investigators.

Patient population – inclusion and exclusion criteria

Subjects meeting all of the following criteria will be considered for inclusion in the trial:

  • 1
    age 61-years or older, either sex
  • 2
    clinical signs and symptoms of an unilateral MCA infarct
  • 3
    National Institutes of Health Stroke Scale (NIHSS) score >14 (infarcts of the nondominant hemisphere) or >19 (infarcts of the dominant hemisphere)
  • 4
    level of consciousness on item 1a of the NIHSS>0
  • 5
    symptom onset before <48 h before operation or initiation of conservative treatment
  • 6
    neuroradiological findings (noncontrast computed tomography or magnetic resonance imaging): unilateral ischaemic infarction of at least two-thirds of the MCA territory, and at least partially including the basal ganglia. Additional involvement of the ACA or PCA territories is optional. These criteria may be evident either in initial neuroimaging or in any follow-up
  • 7
    possibility to start treatment within 6 h after randomisation, and
  • 8
    informed consent by the patient him/herself, his/her legal representative, adjudication by a legally competent judge, or by an independent physician neither involved in the patient's treatment nor the trial.

Subjects presenting with any of the following criteria will not be included in the trial:

  • 1
    premorbid mRS score >1 or premorbid Barthel Index<95
  • 2
    coincidental or timely associated other brain lesion
  • 3
    absence of pupil reflexes
  • 4
    Glasgow Coma Scale (GCS) score <6
  • 5
    secondary space-occupying haemorrhage in the area of infarction (PH2)
  • 6
    known systemic bleeding or coagulation disorder
  • 7
    life expectancy <3-years
  • 8
    other concomitant severe disease that would confound with treatment
  • 9
    other clear contraindication for treatment, and
  • 10
    participation in any other interventional trial.

Screening and randomisation

After admission, clinical examination, neuroimaging, verification of inclusion and exclusion criteria, and informed consent, patients are randomly assigned to one of the two treatment groups (visit 1): (1) conservative treatment alone or (2) hemicraniectomy plus conservative treatment within 48 h of symptom onset. Randomisation of patients in one of the two treatment groups is carried out online (http://www.randomizer.at). In order to ensure a balanced distribution of both therapies in each participating centre, randomisation is stratified for the centre. In case of failure to randomise a patient online, a 24-h/7-day phone service is provided for alternative randomisation by sealed envelopes.

Treatment or intervention

Treatment is started in each group within not later than 48 h after symptom onset and not later than 6 h after randomisation (visit 2).

Decompressive hemicraniectomy consists of a large hemicraniectomy and a duraplasty. In summary, a large (reversed) question-mark-shaped skin incision based at the ear is made from the ipsilateral ear to the occiput, sparing the facial nerve. After separating the temporal muscle and preparation of the galea periost, a bone flap with a diameter of at least 12 cm is removed, including the frontal (up to the middle pupilar line), parietal (up to 2 cm lateral of the sinus sagittalis superior), temporal (down to the base of the middle cranial fossa), and parts of the occipital (up to 4 cm behind the outer ear canal) squamae. If necessary, additional temporal bone is removed so that the floor of the middle cerebral fossa can be explored. The dura is opened and an augmented dural patch, consisting of homologous periost, temporal fascia, or lyophylised cadaver dura is inserted. The dura is fixed at the margin of the craniotomy to prevent epidural bleeding. The temporal muscle and the skin flap are then reapproximated and secured. Resection of necrotic tissue is not recommended, but optional. Insertion of an ICP probe or other monitoring probes is optional but not obligatory. After surgery, patients are transferred to the ICU. In surviving patients, cranioplasty is performed after six-weeks to six-months, using the stored bone flap (at −80°C) or an artificial bone flap.

Conservative treatment: So far, no mode of conservative treatment in malignant MCA infarction has been proven to be effective or superior to another. As a result, treatment options may vary between institutions. The following recommendations are the result of a consensus protocol of all participating centres:

  • 1
    Osmotherapy: osmotherapy may be started at any time point after randomisation. The use of mannitol (20%, 100 ml or 0·5–1·0 g/kg every 4–6 h, maximum 2·5 g/kg/day), glycerol (10%, 250 ml, four times per day), or hydroxyl–ethyl starch (6% in 0·9% saline, 100–250 ml every 8 h, maximum 750 ml/day) is left at the discretion of the treating physician. Dosage depends on serum osmolality, which should reach 315–320 mOsm. In particular, in combination with mannitol and under rigorous control of serum sodium levels, 10% saline (repeatedly administered as 75 ml boluses) may be used.
  • 2
    Intubation and mechanical ventilation: patients should be intubated at a GCS score <8, when there are any signs of respiratory insufficiency (arterial pO2<60 mmHg and/or pCO2>48 mmHg), reduced swallowing or coughing reflexes, or when the airway is compromised. Earlier intubation and mode of ventilation are left at the discretion of the treating physician.
  • 3
    Hyperventilation: the use of hyperventilation is discouraged in the early phase of treatment. In the case of further neurological deterioration and/or uncontrolled increase in ICP, hyperventilation may be started as an ultima ratio. It is advised to monitor venous oxygenation with jugular bulb oxymetry and to maintain saturation above 50%. Arterial pCO2 may be reduced to 28–32 mmHg.
  • 4
    Buffer solution may be used as the last option when other therapeutic attempts have failed. Trimethamin (THAM, Tris buffer) is recommended (1 mmol/kg as bolus over 45 min, followed by 0·25 mmol/kg/h, arterial target pH 7·5–7·55). If ICP does not decrease 10–15 mmHg within 15 min, treatment should be considered as ineffective.
  • 5
    Hypothermia is not recommended within this trial, but is optional.
  • 6
    ICP monitoring: the use and mode of invasive ICP monitoring are left at the discretion of the treating physician. If used, measurement should be performed in the ipsilateral side.
  • 7
    Sedation: the mode of sedation is left at the discretion of the treating physician. The use of barbiturates is discouraged, because they may reduce cerebral perfusion pressure and often do not lead to sustained control of ICP. The use of muscle relaxants is left at the discretion of the treating physician.
  • 8
    Blood pressure control: blood pressure is controlled according to the latest recommendations of the treatment of acute ischaemic stroke (22). The use of catecholamines or antihypertensive drugs is left at the discretion of the treating physician. An exception is made in patients after decompressive surgery. Blood pressure during the first 8 h after surgery is kept at 140–160 mmHg to avoid severe bleedings.
  • 9
    Positioning: flat head positioning is recommended. In patients at risk for aspiration or pneumonia, or after intubation, elevation of the head of 15–30° is recommended.
  • 10
    Body core temperature: normothermia is recommended. Elevated body temperature is treated as soon as it exceeds 37·5°C (22). The use of antipyretics, external cooling, or intravasal cooling is left at the discretion of the treating physician.
  • 11
    Blood glucose level: blood glucose level should not exceed 140 mg/dl (8 mmol/l), with a target level of 80–110 mg/dl using insulin if necessary. Hypoglycaemia is treated with infusion of 10% or 20% glucose solution (22).
  • 12
    Haemoglobin concentration should be above 10 g/dl using erythrocyte concentrates, if necessary.
  • 13
    For prophylaxis of deep venous thrombosis, low-molecular-weight heparins s.c. are recommended.

Intensive care treatment may vary between centres, but has to be standardised within each participating centre. All treatments in the ICU are documented for postprotocol analysis.

The total duration of acute treatment (visits 1 and 2) is individual, usually <2-weeks, but may be longer. According to the trial protocol, visit 2 is followed by two further visits at six-months (visit 3) and one-year (visit 4) after randomisation. These two visits are part of the trial and are performed by investigators, who were not involved in the patient's treatment. The last follow-up will be after one-year for all arms (Table 1).

Table 1.   Procedures of the DESTINY II trial
 Visit 1: screening/ randomisationVisit 2: conservative treatment/ hemicraniectomyVisit 3: follow-up: six-months ± 14-daysVisit 4: follow-up: one-year ± 14-days
  1. a Routine examination . b Premorbid status . c If patient was not capable of giving informed consent previously and has regained his/her capability of giving informed consent.

Age, gender, height, weightXa   
Time and date of symptom onset and admissionXa   
Modified Rankin ScaleXa,b XX
Barthel IndexXa,b  X
NIH Stroke ScaleXa  X
Glasgow Coma ScaleXa   
Neuroimaging (CT, MRT): time and date, infarct localization, infarct size, involvement of ACA/PCA territory, involvement of basal ganglia, contralateral infarct, and parenchymal hematomaXa   
Inclusion/exclusion criteriaX   
Informed consentX XcXc
Randomisation: time and date, random number, and treatment armX   
Treatment: time and date of treatment start, treatment arm X  
Skull reimplantation: time and date   X
SF-36   X
EuroQoL 5D   X
Hamilton Depression Rating Scale   X
Aachener Aphasia Test   X
Agreement to remain in trial  XX
SAE XXX

Primary outcome

Functional outcome according to the mRS score and dichotomised 0–4 vs. 5 or 6, recorded six-months ± 14-days after randomisation (23).

Secondary outcomes

All secondary endpoints are recorded one-year ± 14-days after randomisation.

  • median survival time (time from randomisation to death by any reason on the basis of Kaplan–Meier estimation)
  • overall mortality (death of any reason)
  • time from surgery to bone flap reimplantation
  • rate of surgery-related complications (after initial surgery and after bone flap reimplantaion including surgery-related haemorrhage requiring blood transfusions, anaesthesia-related incidents, pain requiring pharmacological treatment, impaired wound healing or wound infection, liquor fistula, hygroma, or any other secondary complication leading to prolongation of hospitalisation or rehospitalisation)
  • neurological status (NIHSS score) (24)
  • disability (mRS score, distribution, and dichotomisation at 0–4 vs. 5 or 6 and at 0–3 vs. 4–6)
  • activities of daily living (Barthel Index) (25)
  • quality of life (SF-36 and EuroQoL 5D) (26–28)
  • speech and language disturbance (Aachen Aphasia Test) (29)
  • retrospective consent to treatment, and
  • depression (Hamilton Depression Rating Scale) (30).

Data management and monitoring body

All data specified in the trial protocol will be documented in the patient's records and on standardised case report forms (CRFs), available as original with two copies. The investigating physician is responsible for appropriate completion of the form. The Institute of Medical Biometry and Informatics Heidelberg is responsible for database development, data acquisition via double entry, data storage, and validation. Data validation includes controls of completeness, consistence, and plausibility of the data documented in the CRF using a query system between the data management and the investigating physician. After resolution of all queries concerning enrolled patients, the databank is closed (end of the trial) and forwarded to the biometrician for the purpose of evaluation. After finalisation of all evaluations, the final report and all original CRFs are delivered to the principal investigator.

The trial is supervised and monitored by the Coordination Center for Clinical Trial (KKS) Heidelberg including initiation and regular site visits, source data verification, and reports of adverse events. All data management and supervising procedures are performed according to standard operation procedures (SOPs) and in accordance to ICH-GCP Guidelines (E6) and the Declaration of Helsinki.

Statistical methods

Hypotheses

The primary endpoint is a dichotomised endpoint, score on the mRS 0–4 (=success) vs. 5 or 6 (=failure) six-months after randomisation. The two-sided test problem is described as follows:

  • image

or

  • image

pdecompression represents the success rate (mRS score 0–4) after decompressive hemicraniectomy plus conservative treatment, pconservative represents the success rate (mRS score 0–4) after conservative treatment alone, and θ represents the log odds ratio.

Analyses

Planning and analysis of the primary endpoint is performed using the software pest 4·4 (Planning and Evaluation of Sequential Trials, John Whitehead, Hazel Brunier, 1989, The PEST project, University of Reading). The trial is planned as a sequential trial with an inspection after each patient that reaches the primary endpoint.

Before each interim analysis, the assignment to the analysis populations (full analysis set, per protocol set, safety analysis set) will be decided according to the specification given in the analysis plan.

As soon as an interim analysis shows a significant difference of success rates, and at the recommendation of the Data Safety and Monitoring Board (DSMB), the steering committee will stop the trial. Depending on the intermediate results of the sequential analysis, the trial will include a maximum of 160 patients. According to the concept of the triangular test, early stopping of the trial with a nonsignificant result is also possible.

All trial participants who have not reached the primary endpoint at the moment of preliminary evaluation-related or premature termination of the trial are considered as overrunning patients. Their treatment will be continued and evaluated separately. Their data are not part of the final confirmatory analysis but will be evaluated separately and the results will be appended to the results of the final analysis.

For the primary analysis, the triangular test for a binary endpoint according to Whitehead will be applied with a two-sided significance level of α=0·05 and a power of 90%. The confirmatory analysis will be performed on the basis of the full analysis set. Additionally, a per protocol analysis will be carried out that includes all patients without major protocol violations.

Secondary endpoints will be evaluated descriptively. Depending on the scales of the variables, the following characteristics are indicated: mean, standard deviation, median, minimum and maximum, first and third quartile, or absolute and relative frequency. Additional descriptive P-values for group comparisons and corresponding 95% confidence intervals will be given where indicated. Comparability of both treatment groups will be evaluated by a comparison of demographic data and baseline values.

Sample size calculation

According to the available data based on observational studies and case reports until 2007 (90 publications, 1834 patients, 386 of those with individual outcome data, including 106 older than 61-years, 35 of those treated conservatively and 71 by hemicraniectomy), the expected success rate is 8·6% in the conservative arm and 31·0% in the surgical arm, respectively. The absolute difference of success rate is 22·4%, the log odds ratio θ is 1·56.

In a classic study design, the expected difference of the primary endpoint would require the inclusion of 65 patients per arm corresponding to a total number of 130 patients. According to the triangular test for the binary endpoint, the sequential design requires a lower number of patients: a significant difference is expected with a probability of 50% after enrolment of 66 patients (33 per arm), and with a probability of 90% after inclusion of less than 130 patients. The maximum number of cases is 160 (80 per arm).

Duration

Based on the number of patients treated in the participating centres within the past three-years, the estimated number of recruited patients averages five per month after activation of all attending centres. Thus, the duration of the trial is estimated four-years, including initiation and evaluation, or three-years starting with the inclusion of the first patient, respectively.

Study organisation

Steering committee

The steering committee consists of the neurological (Professor Eric Jüttler, principal investigator) and the neurosurgical (Professor Andreas Unterberg) project manager along with the director of the leading trial centre (Professor Werner Hacke). The Steering Committee is responsible for planning of the trial including funding, development of the trial protocol in cooperation with the participating centres, design of patient's and legal representative's information and informed consent, approval of the trial protocol and informed consent including later amendments by legal authorities and ethics committees, selection, verification, and recruitment of potential trial centres, design of the CRF, and organisation of a randomisation system on a 24-h/7-days basis including a trial-phone hotline. Based on the results of the sequential design and the recommendations of the DSMB, the steering committee decides on preliminary termination or continuation of the trial. The steering committee can also stop the trial preliminary, if advised so for other reasons by the DSMB. Furthermore, the steering committee has to give consent to reports and publication of trial results.

DSMB

Safety aspects of the trial are supervised by the DSMB. The DSMB consists of an independent stroke physician (Professor Kennedy Lees, University of Glasgow, UK), neurosurgeon (Professor Peter Hutchinson, University of Cambridge, UK), and epidemiologist (Professor Ale Algra, University of Utrecht, the Netherlands), not involved in the planning or conduction of the trial. The DSMB independently elects a chairman. The DSMB is responsible for critical evaluation and suggestions for improvement of the trial protocol and supervision of the trial course. The DSMB has to be informed about the results of the sequential analysis of the primary endpoint after every 10 patients having reached this endpoint, but at least every six-months starting with the day of inclusion of the first patient, and immediately when there is a statistically significant result concerning the primary endpoint by the responsible biostatistician including the result of the sequential analysis and number of severe adverse events in each of both treatment groups. In case of a significant result ahead of time, the responsible biostatistician has to inform the DSMB immediately. Based on these results of the sequential trial design and safety aspects, the DSMB will recommend to continue or stop the trial. The members of the DMSB confer personally or via telephone and report their recommendations to the steering committee.

The DESTINY II study group

Ten centres are currently participating, eight others are under way:

University of Heidelberg (J. Bösel, Department of Neurology; A. Unterberg, Department of Neurosurgery);

Charité– Universitätsmedizin Berlin [T. Nowe, Center for Stroke Research Berlin (CSB); J. Woitzik, Department of Neurosurgery];

University of Dresden (H. Schneider, Department of Neurology; T. Pinzer, Department of Neurosurgery);

University of Leipzig (D. Schneider, Department of Neurology; J. Meixensberger, Department of Neurosurgery);

University of Erlangen (H.B. Huttner, Department of Neurology; O. Ganslandt, Department of Neurosurgery);

University of Mainz (S. Klimpe, Department of Neurology, T. Kerz, Department of Neurosurgery);

University of Münster (M. Ritter, Department of Neurology, W. Stummer, Department of Neurosurgery);

Medizinische Hochschule Hannover (K. Weissenborn, Department of Neurology, E. Herrmann, Department of Neurosurgery);

University of Freiburg (W.-D. Niessen, Department of Neurology, M. Shah, Department of Neurosurgery);

University of Frankfurt (C. Foerch, Department of Neurology, H. Vatter, Department of Neurosurgery);

University of Munich (LMU) (T. Pfefferkorn, Department of Neurology, A. Peraud, Department of Neurosurgery); and

University of Munich (TU) (H. Poppert, Department of Neurology, M. Stoffel, Department of Neurosurgery).

The DESTINY trial team

J. Bösel, H. Amiri, A. Dormann, P. Beck, Department of Neurology, University of Heidelberg.

Summary and conclusions

  1. Top of page
  2. Abstract
  3. Executive summary
  4. Introduction and rationale
  5. Methods
  6. Summary and conclusions
  7. References

The benefit of hemicraniectomy after malignant MCA infarction in reducing death, without increasing most severe disability, and increasing independency has been demonstrated in patients under 60-years by randomised controlled trials. Although available data from observational studies suggest a reduced benefit of hemicraniectomy in older patients, these data are insufficient for decision making in clinical practice. Owing to the fact that about 50% of patients with malignant MCA infarction are older than 60-years, this question is of great clinical relevance, especially with regard to our ageing population. DESTINY II aims to investigate the benefit of early hemicraniectomy plus conservative treatment vs. conservative treatment alone in a randomised, controlled, multicentre, sequential trial design. The results are expected to answer one of the most urgent questions in the treatment of malignant MCA infarction, thereby directly influencing recommendations for acute stroke treatment. Many open questions such as long-tem retrospective agreement of patients with malignant MCA infarcts and the impact of chronic disability or predicting factors for the development of space-occupying oedema and the benefit from hemicraniectomy, such as neuroimaging findings, timing, and operating techniques, are still unresolved. In order to answer these questions, studies including much larger numbers are needed. Currently, a prospective registry including all patients with large MCA infarcts irrespective of treatment is in a planning status (31).

References

  1. Top of page
  2. Abstract
  3. Executive summary
  4. Introduction and rationale
  5. Methods
  6. Summary and conclusions
  7. References
  • 1
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