Protamine sulfate for Severe aortic stenosis

Inclusion criteria

• {"criterion_text":"- •\tAge ≥55 years\n- •\tSevere aortic stenosis\n- •\tScheduled for transfemoral TAVR\n- •\tWilling to participate, able to understand and to consent, signed informed consent"}

Exclusion criteria

• {"criterion_text":"- •\tPresence of mechanical heart valve\n- •\tPregnant women and women of childbearing potential\n- •\tPrior allergic reaction to protamine or increased anaphylactic risk according to the investigator’s discretion\n- •\tPrior heparin-induced thrombocytopenia\n- •\tKnown heparin allergy\n- •\tPercutaneous coronary intervention within 4 weeks prior to TAVR\n- • 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)\n- •\tPatients on direct oral anticoagulants if not paused on the day of TAVR procedure\n- •\tPatients on vitamin K antagonists if INR > 1.8 before TAVR procedure (last measure-ment within three days prior procedure)\n- •\tSubjects participating in another clinical trial with an investigational new drug or not commercially available and approved devices"}

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Primary: Bleeding grade ≥ type 2 defined by VARC criteria assessed until 60 hours post-TAVR (superiority testing). Key secondary: Major ischemic events until 60 hours post-procedure defined as composite of cardiovascular mortality, myocardial infarction, ischemic stroke, major ischemic vascular complications (non-inferiority testing)."}

Secondary endpoints

• {"endpoint_text":"- •\tIndex-hospital mortality","definition_or_measurement_approach":"Mortality occurring during the index hospitalization."}
• {"endpoint_text":"- •\tAll-cause mortality at 30 days post TAVR procedure","definition_or_measurement_approach":"All-cause mortality assessed at 30 days after the TAVR procedure."}
• {"endpoint_text":"- •\tBleeding grade type 1 (VARC) until 60h post TAVR procedure","definition_or_measurement_approach":"VARC bleeding grade 1 events assessed until 60 hours post-procedure."}
• {"endpoint_text":"- •\tUnplanned cardiac or vascular surgery at 30 days post TAVR procedure","definition_or_measurement_approach":"Occurrence of unplanned cardiac or vascular surgery within 30 days after TAVR."}
• {"endpoint_text":"- •\tMinor vascular complications until 60h post TAVR procedure","definition_or_measurement_approach":"Minor vascular complication events assessed until 60 hours post-procedure."}
• {"endpoint_text":"- •\tMean aortic valve gradient measured by transthoracic echocardiography (TTE) until 60h post TAVR procedure","definition_or_measurement_approach":"Mean aortic valve gradient measured by TTE up to 60 hours after procedure."}
• {"endpoint_text":"- •\tDelta mean aortic valve gradient (before TAVR vs. post TAVR procedure) measured by TTE until 60h post TAVR procedure","definition_or_measurement_approach":"Change in mean aortic valve gradient (pre- vs post-TAVR) measured by TTE within 60 hours post-procedure."}
• {"endpoint_text":"- •\tEvidence of subclinical TAVR valve thrombosis until 60h post TAVR procedure","definition_or_measurement_approach":"Assessment for subclinical valve thrombosis up to 60 hours after TAVR (method not further specified)."}
• {"endpoint_text":"- • Analysis of patients with and without oral anticoagulation with respect to the primary endpoint","definition_or_measurement_approach":"Subgroup analysis comparing patients on oral anticoagulation vs not regarding the primary endpoint."}
• {"endpoint_text":"- • Analysis of patients with single vs. dual antiplatelet therapy with respect to the primary endpoint","definition_or_measurement_approach":"Subgroup analysis of single vs dual antiplatelet therapy on the primary endpoint."}
• {"endpoint_text":"- • Analysis of different vascular closure devices with respect to the primary endpoint","definition_or_measurement_approach":"Subgroup analysis by type of vascular closure device used, effect on primary endpoint."}
• {"endpoint_text":"- • Analysis of different sheath sizes with respect to the primary endpoint","definition_or_measurement_approach":"Subgroup analysis by sheath size used, effect on primary endpoint."}
• {"endpoint_text":"- •\tMaximal drop of hemoglobin level from admission until follow-up until 60h post TAVR procedure","definition_or_measurement_approach":"Maximum decrease in hemoglobin from admission to follow-up measured within 60 hours post-procedure."}
• {"endpoint_text":"- •\tAmount of red blood cell transfusions until 60h post TAVR procedure","definition_or_measurement_approach":"Number/amount of RBC transfusions given up to 60 hours after TAVR."}
• {"endpoint_text":"- •\tPerformance of percutaneous transluminal angioplasty of access site until 60h post TAVR procedure","definition_or_measurement_approach":"Occurrence of percutaneous transluminal angioplasty at access site within 60 hours post-procedure."}
• {"endpoint_text":"- •\tSex-specific analysis of the primary composite endpoint as well as its components","definition_or_measurement_approach":"Sex-stratified analysis of the primary composite endpoint and its individual components."}
• {"endpoint_text":"- •\tSex-specific analysis of all secondary endpoints","definition_or_measurement_approach":"Sex-stratified analysis of all secondary endpoints."}
• {"endpoint_text":"- •\tChange of baseline NYHA class at 30 days post TAVR procedure","definition_or_measurement_approach":"Change in NYHA functional class from baseline to 30 days post-procedure."}
• {"endpoint_text":"- •\tLength of hospital stay after TAVR procedure","definition_or_measurement_approach":"Duration of hospital stay following TAVR (days)."}

Germany

Earliest CTIS Part Ii Submission Date

20-11-2024

Latest Decision Or Authorization Date

19-09-2025

Processing Time Days

303

Number Of Sites

3

Number Of Participants

954

Primary sponsor

Full Name

Klinikum der Universitaet Muenchen AöR

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany

Third parties

• {"country":"Germany","full_name":"Universitaetsklinikum Erlangen AöR","duties_or_roles":"codes: 14","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Deutsches Herzzentrum Muenchen Des Freistaates Bayern Klinik An Der Technischen Universitaet Muenchen","duties_or_roles":"codes: 1,12,5,6,8,9","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Ludwig-Maximilians-Universitaet Muenchen","duties_or_roles":"codes: 10","organisation_type":"Educational Institution"}