Improving Outcome in Subarachnoid Hemorrhage wIth Nadroparine

• Status: Not yet recruiting
• Trial end date: 2024-07-01
• Target enrollment: 0
• Participant gender: All

Summary

Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) was long thought to be caused by subarachnoid blood-induced vasospasm. Experimental and clinical evidence suggest activation of several pathophysiological pathways, affecting the cerebral microcirculation. Recently, lower in-hospital mortality and less non-home discharge was reported in patients treated with therapeutic low-molecular weight heparin (LMWH), compared to patients with standard, prophylactic LMWH, pointing towards a potential benefit of higher doses of LMWH in the acute course after aSAH. Treatment with therapeutic LMWH might improve clinical outcome in endovascularly treated aSAH patients.

The primary objective is to evaluate whether aSAH patients treated with therapeutic LMWH have a lower 30-day mortality rate compared to patients treated with prophylactic LMWH. Secondary objectives are to evaluate whether there are significant differences between patients treated with therapeutic and prophylactic LMWH in development of DCI, (hemorrhagic) complications during admission, hydrocephalus, non-home discharge location, quality of life, clinical outcome and cognitive functioning at three and six months, total health care costs.

A single center, prospective, phase II randomized clinical trial in aneurysmal SAH patients ≥18 years old, in whom the causative aneurysm is treated with endovascular coiling less than 72 hours after initial SAH.

Patients are randomized into 2 groups: (1) Therapeutic dose LMWH group: the standard prophylactic dose, administered upon hospital admission, will be replaced by nadroparin s.c. twice daily 5700 IE anti-Xa, starting within 24 hours after coiling and continued until 21 days after ictus of initial SAH. After 21 days, patients will continue with standard care prophylactic dose until discharge or when mobilized for more than 6 hours per day; (2) Control group: standard of care treatment with prophylactic dose of LMWH; nadroparin, s.c. once daily 2850 AxaIU until discharge or when mobilized for at least 6 hours a day.

Primary outcome: 30-days' mortality. Secondary outcome: DCI, venous thrombo-embolic complications, occurrence of major and non-major bleeding, hemorrhagic complications after external ventricular/lumbar drain (EVD/ELD) placement and lumbar puncture (LP), other SAH-related complications, shunt-dependent hydrocephalus, discharge location, quality of life, total health care costs, cognitive functioning, clinical outcome.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Treatments: Nadroparin

Criteria

Inclusion Criteria:

• SAH confirmed by CT or lumbar puncture with the causative aneurysm confirmed by CT-A and/or digital subtraction angiography

• Coiling of the causative aneurysm within 72 hours of initial SAH

• Informed consent within 24 hours after coiling

Exclusion Criteria:

Stent-assisted coiling

• Use of anticoagulant medication post-coiling for other reasons

• Contra-indications for LMWH:

• Previous history of history of heparin-induced thrombocytopenia

• (Suspicion of) active arterial or venous bleeding

• Previous history of hemorrhagic diathesis due to coagulation disorders (with the ex-ception of disseminated intravascular coagulation)

• Severe hypertension: uncontrolled hypertension with a mean arterial pressure >135mmHg

• Previous history of hypertensive or diabetic retinopathy

• Previous history of active infectious endocarditis

• Severe renal impairment (creatinine clearance <30 mL / min)

• No proficiency of Dutch or English language