1. To study whether minimally invasive endoscopy-guided surgery, in addition to standard medical management, for the treatment of spontaneous supratentorial ICH performed within 8 hours of symptom onset, improves functional outcome in comparison…
ID
Source
Brief title
Condition
- Central nervous system vascular disorders
- Nervous system, skull and spine therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome parameter will be the modified Rankin scale (mRS) score at
180 days. This categorical scale measures functional outcome with scores
ranging from 0 (no symptoms) to 6 (death). The treatment effect will be
estimated with ordinal logistic regression analysis as common odds ratio,
adjusted for prespecified prognostic factors. The adjusted common odds ratio
will measure the likelihood that minimally invasive endoscopy-guided surgery
will lead to lower mRS scores as compared to standard medical management alone.
Secondary outcome
Secondary outcomes will include: the score on the mRS at 90 and 365 days;
favorable outcome (defined as a mRS 0-2 and 0-3) and all other possible
dichotomizations of the mRS at 90, 180 and 365 days; NIHSS at day 6 (±1 day);
death, Barthel Index, EuroQol-5D-5L, SS-QOL, health economic evaluations
(medical consumption, productivity loss and burden for the caregiver), patient
location and home time at 90, 180 and 365 days. Safety outcomes will be death
within 24 hours, at 7 and at 30 days and procedure-related complications within
7 days. Technical effectiveness outcomes will be percentage volume reduction
based on the baseline CT and CT at 24 hours (± 6 hours), percentage of
participants with clot volume reduction >=70%, and >=80%, and with remaining clot
volume <=10mL, and <=15mL, and conversion to craniotomy. In DIST-INFLAME,
outcomes will include perihematomal edema at 6 days (±1 day), functional
outcome at 180 days and immune and metabolomic profiles at 3 (±12 hours) and 6
days (±1 day).
Background summary
Intracerebral hemorrhage (ICH) accounts for 16-19% of all strokes in Western
Europe and contributes profoundly to mortality and disability. Thirty-day case
fatality is 40% and of those surviving, only few gain independence. Except for
stroke unit care and possibly early blood pressure lowering, there is currently
no treatment of proven benefit. Surgical treatment, craniotomy, or minimally
invasive surgery with the administration of alteplase, has so far not been
proven effective. In the largest trials STICH I and II, and MISTIE III, the
median time to treatment was more than 24 hours, which may be an important
explanation for the lack of a treatment effect. A recent meta-analysis of
randomized controlled trials showed that surgical treatment may be beneficial,
in particular with minimally invasive procedures and when performed early. In
the Dutch ICH Surgery pilot study, we showed that early minimally invasive
endoscopy-guided surgical treatment performed within 8 hours of symptom onset
in patients with supratentorial ICH is safe and technically effective. We
hypothesize that early minimally invasive endoscopy-guided surgery improves the
outcome in patients with supratentorial spontaneous ICH.
Study objective
1. To study whether minimally invasive endoscopy-guided surgery, in addition to
standard medical management, for the treatment of spontaneous supratentorial
ICH performed within 8 hours of symptom onset, improves functional outcome in
comparison with standard medical management alone;
2. Determine whether patients treated with minimally invasive surgery develop
less perihematomal edema on non-contrast CT at day 6 (±1 day) than controls,
and whether the CT perfusion permeability surface-area product around the ICH
at baseline modifies this effect (DIST-INFLAME);
3. Compare immune profiles over time in peripheral venous blood between
surgically treated patients and controls (DIST-INFLAME);
4. To assess the cost-effectiveness and budget-impact of minimally invasive
endoscopy-guided surgery for the treatment of spontaneous supratentorial ICH
performed within 8 hours of symptom onset.
Study design
A multicenter, prospective, randomized, open, blinded endpoint (PROBE) clinical
trial.
Intervention
Patients will be randomized (1:1) to minimally invasive endoscopy-guided
surgery performed within 8 hours of symptom onset in addition to standard
medical management or to standard medical management alone.
Study burden and risks
Minimally invasive endoscopy-guided surgery has been shown to carry limited
risks and is of potential benefit to improve outcome, in particular when
performed early. We therefore make use of deferred written informed consent.
The main risks of surgery consist of persistent or recurrent intracranial
hemorrhage, surgical site infection, intracranial infection and seizures.
Besides the intervention for participants randomized to surgical treatment, the
burden for all participants will consist of performing two additional
non-contrast CT scans at 24 hours (± 6 hours) and 6 days (±1 day) after the
baseline non-contrast CT, and a telephone interview for outcome assessment
after 90, 180 and 365 days. Because patients with ICH may present with aphasia
or decreased consciousness, we will include competent and non-competent
patients (consent by proxy). In all participants in the surgical arm, a
non-contrast CT immediately after surgery will be performed, to assess the
achieved reduction in ICH volume. All participants will have blood samples
drawn at baseline. In the participants in the DIST-INFLAME, a CT perfusion-scan
will be performed at baseline and additional blood samples will be drawn on day
3 (±12 hours) and day 6 (±1 day).
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
1. Age 18 years or older;
2. NIHSS >= 2;
3. Supratentorial non-traumatic ICH confirmed by non-contrast CT, without a CTA
confirmed causative vascular lesion (e.g. aneurysm, AVM, DAVF, CVST), or other
known underlying lesion (e.g. tumor, cavernoma);
4. Minimal hematoma volume of 10 mL;
5. Intervention can be started within 8 hours of symptom onset;
6. Written informed consent (deferred).
Exclusion criteria
1. Considerable pre-stroke dependency in activities of daily living, defined as
a pre-stroke mRS >=3;
2. ICH-GS score >=11;
3. Hemorrhage due to hemorrhagic transformation of an infarct;
4. Untreated coagulation abnormalities, including INR >1.3 (point of care
measurement allowed), treatment with heparin and treatment with factor Xa
inhibitors. Patients on vitamin K antagonist can be included after correction
of the INR, and patients on dabigatran (direct thrombin inhibitor) can be
included after reversal of dabigatran with idarucizumab;
5. Moribund (e.g. coning, bilateral dilated unresponsive pupils), or
progressively deteriorating clinical course with imminent death;
6. Pregnancy;
7. DIST-INFLAME (sub-study): patients that use immunosuppressive or
immune-modulating medication.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL80112.078.22 |