Efficacy of daily IV administration of dornase alfa for up to 14 days post subarachnoid haemorrhage on functional independence at 6 months: a multicentre open-label randomised controlled trial of the PROBE type Probe

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hopital Fondation Adolphe De Rothschild

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

15 May 2025 → ongoing

Decision date (initial)

2024-10-31

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

EValuate the efficacy of a daily IV infusion of dornase alfa (125 microg/kg) up to D14 post-HSA on the occurrence of an excellent functional prognosis at 6 months.

Secondary objectives 11

1. Evaluate the efficacy of a daily IV infusion of dornase alfa (125 microg/kg) up to D14 post-HSA on: the incidence of CRF up to D21 post-HSA (or hospital discharge if before D21)
2. Functional prognosis at 6 months
3. The incidence of ischaemic lesions on magnetic resonance imaging (MRI) at D21 after SAH (or the last imaging performed if discharge took place before D21)
4. The need for vasospasm treatment until 21 days after SAH (or discharge from hospital if before 21 days)
5. The total number of days of treatment for vasospasm in the 21 days following SAH (or discharge from hospital if prior to day 21)
6. Cognitive abilities at 6 months
7. Mortality at D21 post-HSA (or at hospital discharge if before D21)
8. The incidence of serious adverse events requiring a change in treatment
9. The evolution of the NETs blood concentration between inclusion and D21 (or discharge if before D21)
10. the specific functional prognosis post-HSA at 6 months
11. Quality of life at 6 months

Conditions and MedDRA coding

subarachnoid hemorrhage

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Patient aged 18 or over
2. Hospital admission for subarachnoid haemorrhage (SAH) due to a ruptured aneurysm
3. Onset of SAH symptoms less than 48 hours old
4. Effective aneurysm exclusion within the last 24 hours
5. No complications during the exclusion procedure, confirmed on post-procedure CT scan
6. Fisher score > 1(présence of blood) on initial brain CT scan before aneurysm exclusion (first scan performed during emergency management)
7. Beneficiary of a social protection scheme
8. Informed consent signed : o By the patient or by a family member/trusted support person if the patient's condition does not allow them to express their consent in writing (L1111-6) o In an emergency situation and in the absence of family members or a trusted support person, the patient may be included. Consent to participate in the research will be sought as soon as the patient's condition allows him/her to express consent.

Exclusion criteria 10

1. Date of unidentified aneurysm rupture
2. Serious infections
3. Patient with renal insufficiency (GFR < 60ml/min/1.73m2 or serum creatinine >130 μmol/L
4. Immediate complications, neurosurgical or related to embolisation
5. Known hypersensitivity to dornase alfa, to Chinese hamster ovary cell products or to the excipients of this product. RESET_protocol_V1.0_Du 20240417 Research code: FDE-2023-11 EU-CTIS 2023-509627-40-00 10/59 product.
6. Previous disability (mRS>1 before SAH)
7. Pregnant or breast-feeding woman (negative urine pregnancy test for women aged 49 or under)
8. Adults subject to a legal protection measure (L1121-8) Persons deprived of their liberty by judicial or administrative decision, persons subject to psychiatric care under articles L3212-1 and L3123-1 and persons admitted to a health or social establishment for purposes other than research (L1121-6).
9. Participation in another interventional drug or medical device clinical trial in the 30 days prior to inclusion.
10. Rebleeding after admission confirmed by a second scan.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Excellent functional prognosis defined by a score of 0 or 1 on the modified Rankin Scale (mRS) at 6 months. Assessment will be centralised and carried out by telephone by a certified professional, blinded to the randomisation arm.

Secondary endpoints 11

1. Focal neurological deficit or decrease in Glasgow score (at least 2 points for at least 1 hour), not immediately after aneurysmal occlusion and not entirely related to another cause (verified by clinical, biological and radiological means), according to the SAHIT (Subarachnoid Hemorrhage International Trialists) definition.
2. Modified Rankin Scale (mRS) score at 6 months
3. Ischaemic lesions on MRI at D21 post-HSA (or at discharge if before D21). MRI scans will be analysed centrally by a radiologist blinded to the randomisation arm.
4. Treatment of vasospasm defined by one of the following interventions: endovascular treatment or IV infusion of milrinone or increase in blood pressure by vasopressor drugs.
5. Number of days among the 21 days post-HSA (or discharge from hospital if before D21) with prescription of one or more of the treatments mentioned in criterion 4
6. MoCA-5min score at 6 months
7. All-cause mortality at D21 (or at hospital discharge if before D21)
8. Serious adverse event
9. Change in NETs blood concentration between sampling at inclusion and sampling at D21 (or at discharge if before D21).
10. Score on the Subarachnoid Haemorrhage-Specific Outcome Tool (SAHOT) scale at 6 months
11. Score on the Stroke Impact Scale-16 (SIS-16) at 6 months

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hopital Fondation Adolphe De Rothschild

Sponsor organisation

Hopital Fondation Adolphe De Rothschild

Address

29 Rue Manin

City

Paris

Postcode

75019

Country

France

Scientific contact point

Organisation

Hopital Fondation Adolphe De Rothschild

Contact name

Amélie Yavchitz

Public contact point

Organisation

Hopital Fondation Adolphe De Rothschild

Contact name

Amélie Yavchitz

Locations

1 EU/EEA country · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications