Fight INflammation to Improve Outcome After Aneurysmal Subarachnoid HEmorRhage

Phase 3

Recruiting

• Conditions: Aneurysmal Subarachnoid Hemorrhage
• Interventions: Drug: Placebo; Drug: Dexamethasone

• Registration Number: NCT05132920
• Lead Sponsor: University Hospital, Bonn

Brief Summary

Aneurysmal subarachnoid hemorrhage (SAH) is a fatal disease with high morbidity and mortality. While the primary injury results from the initial bleeding and cannot be influenced, secondary injury through vasospasms and delayed cerebral ischemia (DCI) during the course of the disease might be a target for intervention in order to improve outcome. To date, beside the aneurysm treatment to prevent re-bleeding and the administration of oral nimodipine, there is no causal therapy available, so that novel treatment concepts are desperately needed. There are strong indications that inflammation contributes to DCI and therefore poor outcome and plays a major role in SAH. Some studies suggest a beneficial effect of anti-inflammatory drugs like glucocorticoids (GC) in SAH patient, but there are no data from randomized controlled trials proving or disproving the beneficial effect of GC, so that current guidelines do not recommend the use of GC in SAH so far.

This multi-center trial aims to generate the first confirmatory data in a controlled randomized fashion that dexamethasone (DEX) improves the outcome in a clinically relevant endpoint in SAH patients. Moreover, this trial will generate first data in a secondary analysis, whether the initial inflammatory state of SAH patients defines a subgroup that particularly responds to a treatment with DEX.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-11-02
• Study First Submitted QC: 2021-11-12
• Study First Posted: 2021-11-24
• Study Start: 2021-12-03
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-08
• Last Update Posted: 2023-05-10
• Primary Completion: 2024-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 334

Inclusion Criteria

1. Male or female subjects, equal or older than 18 years old
2. Written consent to participate in the study by the patient or his legal representative (emergency inclusion by next of kin or consultant physician under the responsibility of the principal investigator is possible)
3. Confirmed diagnosis of aneurysmal SAH and onset within 48 hours before inclusion.

Exclusion Criteria

1. SAH due to any other cause than aneurysm rupture (e.g. traumatic, arteriovenous malformation (AVM), fistula, dissection)
2. Any condition that, in the judgement of the Investigator, could impose hazards to the patient if study therapy is initiated or affects the participation of the patient in the study
3. Patients with obvious evidence of irreparable brainstem or thalamic injury
4. Patients with foreseeable difficulties to attend follow-ups adequately
5. Subjects with a physical or psychiatric condition which at the investigator's discretion may put the subject at risk, may confound the trial results, or may interfere with the subject's participation in this clinical trial
6. Current positive pregnancy test (e.g. β-HCG test in serum)
7. Known history of hypersensitivity to the investigational drug or to drugs with a similar chemical structure
8. Severe infectious diseases
9. Known angle-closure or open angle glaucoma
10. Known ulceration in the gastro-intestinal tract
11. History of gastro-intestinal bleeding
12. Long-term treatment with corticosteroids prior SAH

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control arm	Placebo	3 x 2 ml Placebo daily for days 1-7 and 1 x 2 ml Placebo daily for days 8-21 in addition to aneurysm treatment and best medical intensive care of SAH patients
Experimental arm	Dexamethasone	3 x 8 mg (2 ml) dexamethasone daily for days 1-7 and 1 x 8 mg (2 ml) dexamethasone daily for days 8-21 in addition to aneurysm treatment and best medical intensive care of SAH patients

Primary Outcome Measures

Name	Time	Method
modified Rankin Scale (mRS) at 6 months after SAH	6 months	Dichotomized modified Rankin Scale (mRS) 6 months after subarachnoid haemorrhage. The dichotomization will be done in the classes "favourable" (mRS 0-3) versus "unfavourable " (mRS 4-6) outcome.

Trial Locations

Locations (13)

Otto von Guericke University Magdeburg; 🇩🇪 Magdeburg, Sachsen-Anhalt, Germany

University Hospital Bonn; 🇩🇪 Bonn, NRW, Germany

University Hospital Leipzig; 🇩🇪 Leipzig, Sachsen, Germany

Klinikum rechts der Isar, School of Medicine, Technical University of Munich; 🇩🇪 München, Bayern, Germany

Johann Wolfgang Goethe-Universität Frankfurt am Main; 🇩🇪 Frankfurt, Hessen, Germany

Eberhard Karls University of Tübingen; 🇩🇪 Tübingen, Baden Württemberg, Germany

Hannover Medical School; 🇩🇪 Hannover, Niedersachsen, Germany

Charité-Universitätsmedizin Berlin; 🇩🇪 Berlin, Germany

University Medical Center Hamburg-Eppendorf; 🇩🇪 Hamburg, Germany

University Medical Center Regensburg; 🇩🇪 Regensburg, Bayern, Germany

University of Ulm/BKH Günzburg; 🇩🇪 Günzburg, Bayern, Germany

University Hospital of Essen; 🇩🇪 Essen, NRW, Germany

University of Cologne; 🇩🇪 Köln, NRW, Germany