Evaluation of the efficacy of intra venous dornase alfa (Pulmozyme®) on arterial recanalization in post-thrombectomy angiography in patients managed for ischemic stroke with thrombolysis and eligible for thrombectomy: a single-center phase II trial.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondation A De Rothschild

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10], Diseases [C] - Cardiovascular Diseases [C14], Analytical,Diagnostic,Therapeutic Techniques and Equipment [E]-Surgical Procedures, Operative [E04]

Trial duration

19 Aug 2022 → 29 Oct 2025

Decision date (initial)

2024-07-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-515831-31-00

EudraCT number

2021-000939-31

ClinicalTrials.gov

NCT04785066

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate in patients managed for ischemic stroke by thrombolysis and eligible for thrombectomy, the efficacy of dornase alfa (Pulmozyme®) intravenous administration on arterial recanalization in post-thrombectomy angiography.

Secondary objectives 12

1. To evaluate in patients managed for ischemic stroke with thrombolysis and eligible for thrombectomy, the efficacy of IV administration of dornase alfa on the rate of early recanalization on pre-thrombectomy angiography
2. To evaluate, in patients managed for ischemic stroke with thrombolysis and eligible for thrombectomy, the efficacy of IV administration of dornase alfa on improving the recanalization rate between the last mechanical thrombectomy pass and one hour after dornase alfa administration (for mechanical thrombectomy procedures <1h).
3. Evaluate in patients managed for ischemic stroke with thrombolysis and eligible for thrombectomy, the efficacy of IV administration of dornase alfa on the duration of the thrombectomy procedure
4. To evaluate, in patients managed for ischemic stroke with thrombolysis and eligible for thrombectomy, the efficacy of IV administration of dornase alfa on the number of thrombectomy passages
5. To evaluate, in patients managed for ischemic stroke by thrombolysis and eligible for thrombectomy, the efficacy of IV administration of dornase alfa on the occurrence of an embolus in a new territory per-procedure of mechanical thrombectomy
6. To evaluate, in patients managed for ischemic stroke with thrombolysis and eligible for thrombectomy, the efficacy of IV administration of dornase alfa on final cerebral infarct volume.
7. To evaluate in patients managed for ischemic stroke with thrombolysis and eligible for thrombectomy, the efficacy of IV administration of dornase alfa on the rate of hemorrhagic transformations at 24h
8. Evaluate in patients managed for ischemic stroke with thrombolysis and eligible for thrombectomy, the efficacy of IV administration of dornase alfa on neurological outcome at 24h
9. Evaluate in patients managed for ischemic stroke with thrombolysis and eligible for thrombectomy, the efficacy of IV administration of dornase alfa on functional prognosis at 3 months
10. To evaluate in patients managed for ischemic stroke with thrombolysis and eligible for thrombectomy, the efficacy of IV administration of dornase alfa on all-cause mortality at 3 months
11. Evaluate in patients managed for ischemic stroke with thrombolysis and eligible for thrombectomy, the efficacy of IV administration of dornase alfa on thrombolysis blood markers
12. Evaluate the efficacy of IV administration of dornase alfa on the occurrence of adverse events and effects in patients managed for ischemic stroke with thrombolysis and eligible for thrombectomy

Conditions and MedDRA coding

Ischemic stroke

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Patient aged over 18
2. Ischaemic stroke due to proximal intracranial occlusion (internal carotid artery or middle cerebral artery in its M1 segment) isolated from the anterior circulation eligible for cerebral thrombectomy.
3. Transferred urgently to the NRI unit at the Fondation Adolphe de Rothschild Hospital for cerebral thrombectomy
4. Treated with intravenous thrombolysis (Alteplase or Tenecteplase) according to the 2021 recommendations of the European Stroke Organisation (ESO) with a bolus performed less than 90 minutes before inclusion
5. With a DWI-ASPECT score ≥ 5 on initial brain MRI
6. Having received complete information about the study and having signed a consent to participate in the study (if it is impossible to provide information and to obtain consent to participate from the person undergoing the research, the information and consent must be obtained from the trusted support person or a family member if present; by way of derogation, inclusion may be carried out by the doctor following an emergency inclusion procedure)
7. Member or beneficiary of a social security scheme

Exclusion criteria 8

1. Tandem occlusion defined by proximal intracranial occlusion associated with homolateral extracranial stenosis of the internal carotid artery (>90% stenosis or complete occlusion) on initial MRI
2. Intracranial occlusion with suspected underlying arterial stenosis on initial MRI
3. mRS score > 2
4. Patient benefiting from a legal protection measure
5. Women of childbearing age (15-49)
6. Known allergy to Dornase alfa (Pulmozyme®) or to one of its excipients.
7. Patients included in this study are not allowed to participate in other interventional clinical research
8. Secondary exclusion criteria: Patients who did not receive the experimental treatment. Excluded patients will be replaced

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Complete recanalisation defined by a revised TICI score of 2C or 3 (Appendix 1) on post-MT cerebral angiography. - If the TM procedure is completed before 1 hour after the start of the dornase alfa infusion and the revised TICI score is <3, a second post-MT angiography, 1 hour after the start of the dornase alfa infusion, will be performed to assess the TICI score for the primary endpoint.
2. Complete recanalisation defined by a revised TICI score of 2C or 3 (Appendix 1) on post-MT cerebral angiography. - If the TM procedure is completed before 1 hour after the start of the dornase alfa infusion and the revised TICI score is 3, the immediate post-TM angiography will be used to assess the TICI score for the primary endpoint.
3. Complete recanalisation defined by a revised TICI score of 2C or 3 (Appendix 1) on post-MT cerebral angiography. - If the duration of the TM procedure is > 1 hour after the start of the dornase alfa infusion, the immediate post-TM angiogram will be used to assess the TICI score for the primary endpoint.

Secondary endpoints 12

1. Early recanalisation defined by a revised TICI score of 2b, 2c or 3 on pre-thrombectomy cerebral angiography
2. Improvement of at least one grade in the revised TICI score between cerebral angiography after the last pass of TM and that performed 1 hour after the start of the dornase alfa infusion (for TM procedures <1 hour)
3. Duration of thrombectomy procedure defined by the time (in minutes) between arterial puncture and recanalisation
4. Number of thrombectomy operations
5. Intra-procedural ENT defined by the appearance on cerebral angiography of arterial occlusion in an initially unaffected territory during or at the end of mechanical thrombectomy
6. Cerebral infarct volume measured on cerebral MRI between 24 and 36 hours after thrombolysis
7. Haemorrhagic transformation assessed on a brain scan at 24-36 hours using the ECASS 3 scale (Appendix 2)
8. Decrease in NIHSS score (Appendix 3) > 8 points between the pre-thrombolysis score and the score 24-36 hours after thrombectomy
9. Favourable functional prognosis at 3 months defined by a modified Rankin score of less than 3 (Appendix 4)
10. All-cause death 3 months after ischaemic stroke
11. Changes in concentrations of thrombolysis blood markers (D-dimers, plasmin-antiplasmin complex, DNAse, fibrinogen degradation products, free DNA) between : before Pulmozyme administration (sample taken when the patient arrived in the NRI unit) and after administration (sample taken at the end of thrombectomy)
12. Adverse events and serious/non-serious adverse reactions

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondation A De Rothschild

Sponsor organisation

Fondation A De Rothschild

Address

29 Rue Manin

City

Paris

Postcode

75019

Country

France

Scientific contact point

Organisation

Fondation A De Rothschild

Contact name

Clinical Research Department

Public contact point

Organisation

Fondation A De Rothschild

Contact name

Clinical Research Department

Locations

1 EU/EEA country · 1 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 14 files

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

Application history

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