Frequency of Reduced Leaflet Motion After Surgical Aortic Valve Replacement and Transcatheter Aortic Valve Replacement.

• Sponsor: The Cleveland Clinic (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02696226
• Collaborator: (none)
• Enrollment: 3
• Location: 1
• Arms: 4
• Actual Duration (Months): 17.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a prospective, randomized pilot study in patients undergoing Sugical Aortic Valve Replacement (SAVR) and Transcatheter Aortic Valve Replacement (TAVR) to estimate the incidence of reduced leaflet motion and assess the impact of perioperative anticoagulation on the incidence of reduced leaflet motion.

Condition or Disease	Intervention/Treatment	Phase
Aortic Valve Disorder	Drug: SAVR Warfarin; Drug: SAVR Aspirin; Drug: TAVR Warfarin and clopidogrel; Drug: TAVR Aspirin and clopidogrel	N/A

Detailed Description

This will be a pilot prospective randomized controlled trial.The study will enroll 50 adult patients scheduled to undergo SAVR and 50 adult patients scheduled to undergo TAVR. Subjects who satisfy Inclusion/Exclusion Criteria will be approached for informed consent. Those who give informed consent will be enrolled. After induction of anesthesia, a computer program will be used to randomize patients to one of the 2 treatment groups.

1. SAVR patients will get either Warfarin or aspirin

2. TAVR patients will get either Warfarin or aspirin.

Patients will be seen at 4-6 weeks postoperatively for Transthoracic ECHO (TTE), 4 dimensional (4D), Multidetector computed tomography (MDCT) scan and review of medical history. Phone follow up at 6,9 and 12 months post-operatively.

Data from this pilot study will enable us to determine the feasibility of a larger randomized controlled clinical trial to investigate the phenomenon of reduced leaflet motion/subclinical valve thrombosis and, possibly, its clinical importance

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Diagnostic
• Official Title: A Pilot Study of Subclinical Leaflet Thrombosis in Bioprosthetic Aortic Valves: A Randomized Controlled Trial
• Actual Study Start Date: Feb 1, 2016
• Actual Primary Completion Date: Jul 28, 2017
• Actual Study Completion Date: Jul 28, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SAVR Warfarin Arm Warfarin arm-(target INR of 2-3)	Drug: SAVR Warfarin; Warfarin treatment for 12 weeks with a target INR of 2-3 Warfarin treatment to begin on postoperative day 1-3 according to the patient's clinical status When warfarin treatment is discontinued, patients will be treated according to standard of care (aspirin 81 mg/day) indefinitely; Other Names: Coumadiin
Experimental: TAVR Warfarin and Clopidogrel Arm Warfarin (target INR of 2-3) and Clopidogrel (75mg/day) arm	Drug: TAVR Warfarin and clopidogrel; Begin Warfarin and clopidogrel (75 mg/day) treatment within 1-3 days postop for 12 weeks with a target INR of 2-3 When warfarin is discontinued, begin aspirin (81 mg/day) and continue aspirin/clopidogrel for 12 weeks At 24 weeks, study treatment will end and patients will be treated according to standard of care (aspirin 81 mg/day) indefinitely; Other Names: Coumadin Plavix
Experimental: SAVR Aspirin Arm Aspirin arm (81mg/day)	Drug: SAVR Aspirin; Aspirin (81 mg/day) to begin within 1-3 postoperative days according to the patient's clinical status and continue indefinitely per standard of care.; Other Names: Aspirin
Experimental: TAVR Aspirin and Clopidogrel Arm Aspirin (81mg/day) and Clopidogrel (75mg/day) arm	Drug: TAVR Aspirin and clopidogrel; Aspirin (81 mg/day) and clopidogrel (75 mg/day) in periprocedural period and continue for 24 weeks At 24 weeks, study treatment will end and patients will be treated according to standard of care (aspirin 81 mg/day) indefinitely; Other Names: Plavix

Outcome Measures

Primary Outcome Measures

1. Leaflet Motion [4-6 weeks post procedure]

   Frequency of reduced leaflet motion related to perioperative anticoagulation with warfarin as measured by 4DMCT data. (<50% reduction in motion), moderately reduced (50 to 70% reduction), severely reduced (>70% reduction), or immobile (lack of motion of at least one valve leaflet).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Scheduled for SAVR or TAVR

• Age > 18 years

• Able and willing to give informed consent

• Able and willing to return for follow up

Exclusion Criteria:

• Contraindications to warfarin, Plavix or aspirin

• Pre-existing medical indication for warfarin, Plavix or aspirin

• History of previous cardiac surgery

• History of previous coronary artery stenting

• Requirement for concomitant coronary artery bypass grafting or mitral valve surgery or surgical treatment of an ascending aortic aneurysm

• Contraindications to contrast-enhanced MDCT including anaphylactic iodine allergy, uncontrolled atrial fibrillation, renal dysfunction (GFR < 60 ml/min).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• The Cleveland Clinic

Investigators

• Principal Investigator: Douglas Johnston, M.D., The Cleveland Clinic

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 5, 2016

More Information

Publications

None provided.

• Responsible Party: Douglas Johnston, MD, The Cleveland Clinic
• ClinicalTrials.gov Identifier: NCT02696226
• Other Study ID Numbers: 16-084
• First Posted: Mar 2, 2016
• Last Update Posted: Aug 24, 2018
• Last Verified: Jul 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Aortic Valve Disease; Aspirin; Warfarin; Clopidogrel

Study Results

Participant Flow

Arm/Group Title	SAVR Warfarin Arm	TAVR Warfarin and Clopidogrel Arm	SAVR Aspirin Arm	TAVR Aspirin and Clopidogrel Arm
Arm/Group Description	Warfarin arm-(target INR of 2-3) SAVR Warfarin: Warfarin treatment for 12 weeks with a target INR of 2-3 Warfarin treatment to begin on postoperative day 1-3 according to the patient's clinical status When warfarin treatment is discontinued, patients will be treated according to standard of care (aspirin 81 mg/day) indefinitely	Warfarin (target INR of 2-3) and Clopidogrel (75mg/day) arm TAVR Warfarin and clopidogrel: Begin Warfarin and clopidogrel (75 mg/day) treatment within 1-3 days postop for 12 weeks with a target INR of 2-3 When warfarin is discontinued, begin aspirin (81 mg/day) and continue aspirin/clopidogrel for 12 weeks At 24 weeks, study treatment will end and patients will be treated according to standard of care (aspirin 81 mg/day) indefinitely	Aspirin arm (81mg/day) SAVR Aspirin: Aspirin (81 mg/day) to begin within 1-3 postoperative days according to the patient's clinical status and continue indefinitely per standard of care.	Aspirin (81mg/day) and Clopidogrel (75mg/day) arm TAVR Aspirin and clopidogrel: Aspirin (81 mg/day) and clopidogrel (75 mg/day) in periprocedural period and continue for 24 weeks At 24 weeks, study treatment will end and patients will be treated according to standard of care (aspirin 81 mg/day) indefinitely
Period Title: Overall Study
STARTED	1	0	2	0
COMPLETED	0	0	0	0
NOT COMPLETED	1	0	2	0

Baseline Characteristics

Arm/Group Title	SAVR Warfarin Arm	TAVR Warfarin and Clopidogrel Arm	SAVR Aspirin Arm	TAVR Aspirin and Clopidogrel Arm	Total
Arm/Group Description	Warfarin arm-(target INR of 2-3) SAVR Warfarin: Warfarin treatment for 12 weeks with a target INR of 2-3 Warfarin treatment to begin on postoperative day 1-3 according to the patient's clinical status When warfarin treatment is discontinued, patients will be treated according to standard of care (aspirin 81 mg/day) indefinitely	Warfarin (target INR of 2-3) and Clopidogrel (75mg/day) arm TAVR Warfarin and clopidogrel: Begin Warfarin and clopidogrel (75 mg/day) treatment within 1-3 days postop for 12 weeks with a target INR of 2-3 When warfarin is discontinued, begin aspirin (81 mg/day) and continue aspirin/clopidogrel for 12 weeks At 24 weeks, study treatment will end and patients will be treated according to standard of care (aspirin 81 mg/day) indefinitely	Aspirin arm (81mg/day) SAVR Aspirin: Aspirin (81 mg/day) to begin within 1-3 postoperative days according to the patient's clinical status and continue indefinitely per standard of care.	Aspirin (81mg/day) and Clopidogrel (75mg/day) arm TAVR Aspirin and clopidogrel: Aspirin (81 mg/day) and clopidogrel (75 mg/day) in periprocedural period and continue for 24 weeks At 24 weeks, study treatment will end and patients will be treated according to standard of care (aspirin 81 mg/day) indefinitely	Total of all reporting groups
Overall Participants	1	0	2	0	3
Age (Count of Participants)
<=18 years	0 0%	0 NaN	0 0%	0 NaN	0 0%
Between 18 and 65 years	0 0%	0 NaN	2 100%	0 NaN	2 66.7%
>=65 years	1 100%	0 NaN	0 0%	0 NaN	1 33.3%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 NaN	1 50%	0 NaN	1 33.3%
Male	1 100%	0 NaN	1 50%	0 NaN	2 66.7%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%

Outcome Measures

1. Primary Outcome

Title	Leaflet Motion
Description	Frequency of reduced leaflet motion related to perioperative anticoagulation with warfarin as measured by 4DMCT data. (<50% reduction in motion), moderately reduced (50 to 70% reduction), severely reduced (>70% reduction), or immobile (lack of motion of at least one valve leaflet).
Time Frame	4-6 weeks post procedure

Outcome Measure Data

Analysis Population Description

Study terminated

Arm/Group Title	SAVR Warfarin Arm	TAVR Warfarin and Clopidogrel Arm	SAVR Aspirin Arm	TAVR Aspirin and Clopidogrel Arm
Arm/Group Description	Warfarin arm-(target INR of 2-3) SAVR Warfarin: Warfarin treatment for 12 weeks with a target INR of 2-3 Warfarin treatment to begin on postoperative day 1-3 according to the patient's clinical status When warfarin treatment is discontinued, patients will be treated according to standard of care (aspirin 81 mg/day) indefinitely	Warfarin (target INR of 2-3) and Clopidogrel (75mg/day) arm TAVR Warfarin and clopidogrel: Begin Warfarin and clopidogrel (75 mg/day) treatment within 1-3 days postop for 12 weeks with a target INR of 2-3 When warfarin is discontinued, begin aspirin (81 mg/day) and continue aspirin/clopidogrel for 12 weeks At 24 weeks, study treatment will end and patients will be treated according to standard of care (aspirin 81 mg/day) indefinitely	Aspirin arm (81mg/day) SAVR Aspirin: Aspirin (81 mg/day) to begin within 1-3 postoperative days according to the patient's clinical status and continue indefinitely per standard of care.	Aspirin (81mg/day) and Clopidogrel (75mg/day) arm TAVR Aspirin and clopidogrel: Aspirin (81 mg/day) and clopidogrel (75 mg/day) in periprocedural period and continue for 24 weeks At 24 weeks, study treatment will end and patients will be treated according to standard of care (aspirin 81 mg/day) indefinitely
Measure Participants	0	0	0	0

Adverse Events

Time Frame	1 year
Adverse Event Reporting Description	Only 2 arms of the trial had enrollment (SAVR Warfarin / SAVR Aspirin). Adverse event information is reported only for these arms
Arm/Group Title	SAVR Warfarin Arm		TAVR Warfarin and Clopidogrel Arm		SAVR Aspirin Arm		TAVR Aspirin and Clopidogrel Arm
Arm/Group Description	Warfarin arm-(target INR of 2-3) SAVR Warfarin: Warfarin treatment for 12 weeks with a target INR of 2-3 Warfarin treatment to begin on postoperative day 1-3 according to the patient's clinical status When warfarin treatment is discontinued, patients will be treated according to standard of care (aspirin 81 mg/day) indefinitely		Warfarin (target INR of 2-3) and Clopidogrel (75mg/day) arm TAVR Warfarin and clopidogrel: Begin Warfarin and clopidogrel (75 mg/day) treatment within 1-3 days postop for 12 weeks with a target INR of 2-3 When warfarin is discontinued, begin aspirin (81 mg/day) and continue aspirin/clopidogrel for 12 weeks At 24 weeks, study treatment will end and patients will be treated according to standard of care (aspirin 81 mg/day) indefinitely		Aspirin arm (81mg/day) SAVR Aspirin: Aspirin (81 mg/day) to begin within 1-3 postoperative days according to the patient's clinical status and continue indefinitely per standard of care.		Aspirin (81mg/day) and Clopidogrel (75mg/day) arm TAVR Aspirin and clopidogrel: Aspirin (81 mg/day) and clopidogrel (75 mg/day) in periprocedural period and continue for 24 weeks At 24 weeks, study treatment will end and patients will be treated according to standard of care (aspirin 81 mg/day) indefinitely
All Cause Mortality
	SAVR Warfarin Arm		TAVR Warfarin and Clopidogrel Arm		SAVR Aspirin Arm		TAVR Aspirin and Clopidogrel Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/0 (NaN)		0/2 (0%)		0/0 (NaN)
Serious Adverse Events
	SAVR Warfarin Arm		TAVR Warfarin and Clopidogrel Arm		SAVR Aspirin Arm		TAVR Aspirin and Clopidogrel Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/0 (NaN)		0/2 (0%)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	SAVR Warfarin Arm		TAVR Warfarin and Clopidogrel Arm		SAVR Aspirin Arm		TAVR Aspirin and Clopidogrel Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/0 (NaN)		0/2 (0%)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.