ATLANTIS Protamine - Antagonization of heparin with protamine sulfate to reduce all neurologic ischemic and hemorrhagic events after transcatheter aortic valve implantation for aortic stenosis: the ATLANTIS Protamine study.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris, Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

24 May 2025 → ongoing

Decision date (initial)

2023-12-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Ministry of Health - PHRC N-20-0735

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To demonstrate the superiority of systematic antagonization with protamine sulfate over usual of care to reduce in-hospital mortality, vascular/bleeding complications, stroke and TIA, myocardial infarction or red blood cell transfusion, from randomization to hospital discharge.

Secondary objectives 3

1. To demonstrate whether systematic heparin antagonization is associated with a shorter hospital stay.
2. • To demonstrate whether systematic heparin antagonization is associated with:- -Less risk of bleeding vascular or ischemic complications -Less acute kidney injury,
3. • To test whether there is an interaction according to the use or not of an echo-guided femoral puncture and/or radial approach as the secondary arterial access site.

Conditions and MedDRA coding

Any patients ≥18 years old, eligible for transfemoral TAVI with coverage for medical insurance

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. • Men and women ≥18 years of age
2. • Any patient eligible for transfemoral TAVI, irrespective of the chronic antithrombotic treatment
3. • Written informed consent
4. • Registered at the French social healthcare

Exclusion criteria 12

1. • Any major protamine sulfate exposure contraindications defined as a history of severe pulmonary hypertension, acute pulmonary edema or history of bronchospasm related to protamine sulfate administration
2. • Known allergy to protamine sulfate
3. • Hypersensitivity to protamine sulfate including protamine contained as an excipient in NPH [Neutral Protamine Hagedorn] insulin, known protamine or protamine-heparine complex antibodies
4. • Non-femoral approach for the TAVI procedure
5. • Protamine sulfate exposure within 24h of randomization
6. • Fish allergy
7. • Mechanical valves
8. • For men: Sterile or Vasectomy
9. • Women of childbearing potential
10. • Pregnancy and breast feeding women
11. • Contemporaneous enrolment in an interventional clinical trial
12. • Patient under guardianship or curatorship

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is defined as the first occurrence, from procedure to hospital discharge, of any event of the composite of all-cause mortality, type 2, 3 or 4 bleeding, major or minor vascular complications, stroke or TIA, myocardial infarction or any red-blood transfusion. The primary endpoint will be blindly determined by a clinical event committee according to the valve Academic Research Consortium-3 (VARC-3 classifications)

Secondary endpoints 4

1. Assessment of length of in-hospital stay in days post TAVI procedure
2. Assessment of the occurrence from procedure to hospital discharge of: Type 2, 3 or 4 bleeding according to the VARC 3 criteria or any red blood cell transfusion of minor or vascular complications. Type 2, 3 or 4 bleedings or red blood cell transfusion. Any red blood cell transfusion Type 2, 3 or 4 bleedings
3. Assessment of an interaction in the impact of systematic antagonization according to the use or not of an echo-guided femoral puncture and/or arterial radial access. These subgroups are defined at the time of randomization by stratification.
4. Assessment of the occurrence from procedure to hospital discharge of: Death or type 2, 3 or 4 bleedings Any kidney injury, stage 2 to 4 according to the KDIGO definition Death, type 2, 3 or 4 bleedings or stroke De a th, VARC 3 type 2-3-4 bleeding or Any red blood cell transfusion, MI or stroke Or TIA Any myocardial infarction, stroke or TIA Type 3 or 4 bleeding Type 2 bleeding Minor vascular complications Access site and access related vascular injury according to VARC-3 criteria

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr Paul Guedeney

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr Paul Guedeney

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

1 Avenue Claude Vellefaux

City

Paris

Postcode

75010

Country

France

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Application history

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