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Strategies to Prevent Transcatheter Heart Valve Dysfunction in Low Risk Transcatheter Aortic Valve Replacement

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ClinicalTrials.gov Identifier: NCT03557242
Recruitment Status : Not yet recruiting
First Posted : June 14, 2018
Last Update Posted : June 14, 2018
Sponsor:
Information provided by (Responsible Party):
Medstar Health Research Institute

Brief Summary:
100 subjects in the each of the treatment arms of the study (total 200 treatment arm subjects) and up to 100 subjects in the registry arm of the study.

Condition or disease Intervention/treatment Phase
Aortic Stenosis Device: TAVR Other: Warfarin plus Aspirin Other: Aspirin Only Not Applicable

Detailed Description:

This study aims to examine the optimal anticoagulation/antiplatelet regimen in low risk patients undergoing TAVR. The prospective randomized controlled arm of this study will assess the utility of short-term oral anticoagulation with warfarin compared to antiplatelet therapy alone after TAVR in low risk patients to reduce the incidence of structural valve deterioration manifest as clinical events, increased aortic valve gradients or transvalvular regurgitation, or subclinical leaflet thrombosis. Low risk subjects with symptomatic severe aortic stenosis will be enrolled to undergo TAVR. Following TAVR, subjects will be randomized to receive warfarin plus low dose Aspirin or low dose Aspirin monotherapy for 30-45 days. Subjects with other indications for anticoagulation (e.g. AF, DVT or PE) will not be randomized and instead will be followed in a separate registry arm. Baseline demographic, clinical, non-invasive imaging (echocardiography and CT), TAVR procedural details, clinical follow up data will be prospectively collected for all subjects. Echocardiography and contrast-enhanced 4D cardiac CT will be performed in all subjects between 30-45 days after TAVR to evaluate for evidence of structural valve deterioration.

This multicenter prospective randomized study will enroll 200 consecutive low risk subjects with symptomatic severe aortic stenosis into the treatment arms of the study. Up to 100 additional subjects with a pre-existing indication for anticoagulation (e.g. atrial fibrillation, deep venous thrombosis or pulmonary embolism) or who are not eligible for randomization after TAVR due to development of a new indication for anticoagulation will be enrolled into the registry arm of the study.

Inclusion of this registry arm will ensure that the secondary objective pooled analysis of patient level data from this study and the Low Risk TAVR (LRT) study, truly represents an all-comers cohort of low risk patients undergoing TAVR, and does not exclude a significant subgroup.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Strategies to Prevent Transcatheter Heart Valve Dysfunction in Low Risk Transcatheter Aortic Valve Replacement
Estimated Study Start Date : June 30, 2018
Estimated Primary Completion Date : July 30, 2023
Estimated Study Completion Date : July 30, 2023


Arm Intervention/treatment
Warfarin plus Aspirin
100 subjects will be randomized electronically through the Electronic Data Capture System in a 1:1 fashion to warfarin plus low dose aspirin for 30-45 days
Device: TAVR
Transcatheter Aortic Valve Replacement

Other: Warfarin plus Aspirin
Subjects randomized to this arm will receive Warfarin plus aspirin for 30- 45 days post TAVR

Aspirin Monotherapy
100 subjects will be randomized electronically through the Electronic Data Capture System in a 1:1 fashion to low dose aspirin monotherapy for 30-45 days
Device: TAVR
Transcatheter Aortic Valve Replacement

Other: Aspirin Only
Subjects randomized to this arm will receive aspirin only post TAVR

Registry Arm
Upto an additional 100 subjects with preexisting indication for anti coagulation (e.g. atrial fibrillation, deep venous thrombosis, pulmonary embolism) or who are not eligible for randomization after TAVR due to development of a new indication for anti coagulation will be enrolled in the registry arm of the study.
Device: TAVR
Transcatheter Aortic Valve Replacement




Primary Outcome Measures :
  1. All Cause Mortality [ Time Frame: 30 days ]
  2. All Stroke [ Time Frame: 30 days ]
    disabling and non-disabling, ischemic, hemorrhagic

  3. Life-threatening and Major Bleeding [ Time Frame: 30 days ]
  4. Major Vascular Complications [ Time Frame: 30 Days ]
  5. Hospitalizations for valve-related symptoms or worsening congestive heart failure [ Time Frame: 30 days ]
  6. Hypoattenuated leaflet thickening (HALT) [ Time Frame: 30 days ]
  7. At least moderately restricted leaflet motion (RELM) [ Time Frame: 30 days ]
  8. Hemodynamic dysfunction [ Time Frame: 30 Days ]
    (mean aortic valve gradient ≥20 mm Hg, AND/OR EOA ≤1.0 cm2 AND/OR DVI<0. 35, AND/OR moderate or severe prosthetic valve regurgitation)


Secondary Outcome Measures :
  1. VARC-2 device success: [ Time Frame: 1 year ]
    • Absence of procedural mortality AND
    • Correct positioning of a single prosthetic heart valve into the proper anatomical location AND
    • Intended performance of the prosthetic heart valve (no prosthesis-patient mismatch and mean aortic valve gradient<20 mm Hg or peak velocity<3 m/s, AND no moderate or severe prosthetic valve regurgitation)

  2. All-cause mortality [ Time Frame: 1 year ]
  3. All stroke [ Time Frame: 1 year ]
    (disabling and non-disabling, ischemic and hemorrhagic)

  4. Life-threatening and major bleeding [ Time Frame: 1 year ]
  5. Major vascular complications [ Time Frame: 1 year ]
  6. Hospitalizations for valve-related symptoms or worsening congestive heart failure [ Time Frame: 1 year ]
  7. Acute kidney injury [ Time Frame: 1 year ]
  8. Pacemaker implantation [ Time Frame: 1 year ]
  9. Endocarditis [ Time Frame: 1 year ]


Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Severe, degenerative AS, defined as:
  • Mean aortic valve gradient ≥40 mm Hg OR Vmax ≥4 m/sec AND
  • Calculated aortic valve area ≤1.0 cm2 OR aortic valve area index ≤0.6 cm2/m2
  • Symptomatic AS, defined as a history of at least one of the following:
  • Dyspnea that qualifies at New York Heart Association (NYHA) class II or greater
  • Angina pectoris
  • Cardiac syncope
  • The Heart Team agrees that the patient is low-risk, quantified by an estimated risk of death ≤3% by the calculated STS score for operative mortality at 30 days; AND agrees that SAVR would be an appropriate therapy if offered
  • A surgeon who is experienced in Surgical Aortic Valve Replacement (SAVR) has spoken with the patient in person and stipulates that the patient understands his/her alternatives for FDA approved therapy, including open heart surgery to replace their aortic valve
  • The institutional Heart Team determines that transfemoral TAVR is appropriate
  • Aortic valve anatomy and dimensions suitable for TAVR using a commercially available valve
  • Iliofemoral artery anatomy and dimensions suitable for transfemoral TAVR using a commercially available valve and delivery system
  • Procedure status is elective
  • Expected survival is at least 24 months

Exclusion Criteria:

  • Subject unable or unwilling to give informed consent
  • Concomitant disease of another heart valve or the aorta that requires either transcatheter or surgical intervention
  • Any condition that is considered a contraindication for placement of a bioprosthetic aortic valve (e.g. patient requires a mechanical aortic valve)
  • Aortic stenosis secondary to a bicuspid aortic valve
  • Prior bioprosthetic surgical aortic valve replacement
  • Mechanical heart valve in another position
  • End-stage renal disease requiring hemodialysis or peritoneal dialysis, or a creatinine clearance <20 cc/min
  • Left ventricular ejection fraction <20%
  • Recent (<6 months) history of stroke
  • Symptomatic carotid or vertebral artery disease, or recent (<6 weeks) surgical or endovascular treatment of carotid stenosis
  • Any contraindication to oral antiplatelet or anticoagulation therapy following the procedure, including recent or ongoing bleeding, or HASBLED score >3 (Table 2 - HASBLED scoring system)
  • Severe coronary artery disease that is unrevascularized
  • Recent (<30 days) acute myocardial infarction
  • Patient cannot undergo transfemoral TAVR for anatomic reasons (as determined by supplemental imaging studies); this would include inadequate size of iliofemoral access vessels or an aortic annulus size that is not accommodated by the commercially available valves
  • Any comorbidity not captured by the STS score that would make SAVR high risk, as determined by a cardiothoracic surgeon who is a member of the heart team; this includes:
  • Porcelain or severely atherosclerotic aorta
  • Frailty
  • Hostile chest
  • Internal mammary artery or other conduit either crosses midline of sternum or is adherent to sternum
  • Severe pulmonary hypertension (PA systolic pressure > 2/3 of systemic pressure)
  • Severe right ventricular dysfunction
  • Ongoing sepsis or infective endocarditis
  • Severe chronic obstructive pulmonary disease, as demonstrated by forced expiratory volume (FEV1) <750 cc
  • Liver failure with Childs class C or D
  • Pre-procedure shock, inotropes, mechanical assist device, or cardiac arrest
  • Pregnancy or intent to become pregnant prior to completion of all protocol follow-up procedures
  • Known allergy to warfarin or aspirin

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03557242


Contacts
Contact: Roshni S Bastian, MPH, MBA 2028777752 roshni.s.bastian@medstar.net
Contact: Rebecca Torguson, MPH 2028772194 rebecca.torguson@medstar.net

Sponsors and Collaborators
Medstar Health Research Institute
Investigators
Principal Investigator: Ron S Waksman, MD MedStar Cardiovascular Research Network

Responsible Party: Medstar Health Research Institute
ClinicalTrials.gov Identifier: NCT03557242     History of Changes
Other Study ID Numbers: LRT 2.0
First Posted: June 14, 2018    Key Record Dates
Last Update Posted: June 14, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No

Additional relevant MeSH terms:
Aortic Valve Stenosis
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction
Aspirin
Warfarin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Anticoagulants