PROTamine Application in patients underGOing tRAnScatheter aortic valve replacement (PROTAGORAS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Klinikum der Universitaet Muenchen AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

28 Mar 2025 → ongoing

Decision date (initial)

2025-01-24

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

LMU University Hospital, LMU Munich (Sponsor) · Else Kröner-Fresenius-Stiftung (EKFS)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To assess the clinical benefit with respect to major bleeding and major ischemic events of post-procedural heparin reversal with protamine after transcatheter aortic valve replacement.

Secondary objectives 1

1. To assess the clinical benefit with respect to mortality, minor bleedings, vascular complications, antiplatelet therapy, hemoglobin, transfusions and sex-specific differences.

Conditions and MedDRA coding

Adult patients with severe aortic stenosis scheduled for transfemoral TAVR

Regulatory references

Scientific advice from competent authorities

Federal Institute For Drugs And Medical Devices

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. • Age ≥55 years
2. • Severe aortic stenosis
3. • Scheduled for transfemoral TAVR
4. • Willing to participate, able to understand and to consent, signed informed consent

Exclusion criteria 10

1. • Presence of mechanical heart valve
2. • Prior allergic reaction to protamine or increased anaphylactic risk according to the investigator’s discretion
3. • Prior heparin-induced thrombocytopenia
4. • Known heparin allergy
5. • Percutaneous coronary intervention within 4 weeks prior to TAVR
6. • Severe TAVR procedure complications (Annulus rupture, aortic dissection, coronary oc-clusion, cardiogenic shock, conversion to open surgery, pericardial tamponade, stroke, valve prosthesis dislocation, mechanical resuscitation not related to bleeding, any other acute TAVR procedure complication considered severe or life threatening by the investigator)
7. • Patients on direct oral anticoagulants if not paused on the day of TAVR procedure
8. • Patients on vitamin K antagonists if INR > 1.8 before TAVR procedure (last measure-ment within three days prior procedure)
9. • Subjects participating in another clinical trial with an investigational new drug or not commercially available and approved devices
10. • Pregnant women and women of childbearing potential

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary and key secondary endpoints (hierarchical testing) are: Primary: Bleeding grade ≥type 2 (VARC) until 60h post TAVR procedure (superiority); Key secondary: Major ischemic events until 60h post procedure (non-inferiority) defined as the composite of Cardiovascular mortality, Myocardial infarction, Ischemic stroke, Major ischemic vascular complications

Secondary endpoints 19

1. • Index-hospital mortality
2. • All-cause mortality at 30 days post TAVR procedure
3. • Bleeding grade type 1 (VARC) until 60h post TAVR procedure
4. • Unplanned cardiac or vascular surgery at 30 days post TAVR procedure
5. • Minor vascular complications until 60h post TAVR procedure
6. • Mean aortic valve gradient measured by transthoracic echocardiography (TTE) until 60h post TAVR procedure
7. • Delta mean aortic valve gradient (before TAVR vs. post TAVR procedure) measured by TTE until 60h post TAVR procedure
8. • Evidence of subclinical TAVR valve thrombosis until 60h post TAVR procedure
9. • Analysis of patients with and without oral anticoagulation with respect to the primary endpoint
10. • Analysis of patients with single vs. dual antiplatelet therapy with respect to the primary endpoint
11. • Analysis of different vascular closure devices with respect to the primary endpoint
12. • Analysis of different sheath sizes with respect to the primary endpoint
13. • Maximal drop of hemoglobin level from admission until follow-up until 60h post TAVR procedure
14. • Amount of red blood cell transfusions until 60h post TAVR procedure
15. • Performance of percutaneous transluminal angioplasty of access site until 60h post TAVR procedure
16. • Sex-specific analysis of the primary composite endpoint as well as its components
17. • Sex-specific analysis of all secondary endpoints
18. • Change of baseline NYHA class at 30 days post TAVR procedure
19. • Length of hospital stay after TAVR procedure

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Klinikum der Universitaet Muenchen AöR

Sponsor organisation

Klinikum der Universitaet Muenchen AöR

Address

Marchioninistrasse 15, Hadern Hadern

City

Munich

Postcode

81377

Country

Germany

Scientific contact point

Organisation

Klinikum der Universitaet Muenchen AöR

Contact name

Sponsor Delegated Person

Public contact point

Organisation

Klinikum der Universitaet Muenchen AöR

Contact name

Clinical Study Group Department of Medicine I LMU Klinikum

Third parties 3

Locations

1 EU/EEA country · 3 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

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