Angiotensin Converting Enzyme (ACE) Inhibition and Cardiac Allograft Vasculopathy

NCT01078363 | Completed Results DMC

• 2 other identifiers: SU-12162009-456216155 (William Fuller Fearon)
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 2

Brief Summary

Cardiac transplantation is the ultimate treatment option for patients with end stage heart failure. Cardiac allograft vasculopathy remains a leading cause of morbidity and mortality after transplantation. Angiotensin converting enzyme inhibitors are used in less than one half of transplant recipients. Preliminary data suggest that angiotensin converting enzyme inhibitors retard the atherosclerotic plaque development that is the hallmark of cardiac allograft vasculopathy. Moreover, this class of drug appears to increase circulating endothelial progenitor cell number and has anti-inflammatory properties, both of which improve endothelial dysfunction, the key precursor to the development of cardiac allograft vasculopathy. The objective of this project is to investigate the role of an angiotensin converting enzyme inhibitor, ramipril, in preventing the development of cardiac allograft vasculopathy. During the first month after cardiac transplantation subjects will undergo coronary angiography with intravascular ultrasound measurements of plaque volume in the left anterior descending coronary artery. Using a coronary pressure wire, epicardial artery and microvascular physiology will be assessed. Finally, endothelial function and mediators of endothelial function, including circulating endothelial progenitor cells, will be measured. Subjects will then be randomized in a double blind fashion to either ramipril or placebo. After 1 year, the above assessment will be repeated. The primary endpoint will be the development of cardiac allograft vasculopathy based on intravascular ultrasound-derived parameters. The second aim will be to assess the effect of ramipril on endothelial dysfunction early after transplantation. The final aim is to determine the impact of ramipril on coronary physiology early after transplantation.

Conditions

Cardiac Allograft Vasculopathy

Keywords

Heart Transplantation

Outcome Measures

Primary Outcomes (1)

• Cardiac Allograft Vasculopathy(CAV) Defined as Change in IVUS-assessed Plaque Volume From Baseline to One Year

  also called transplant coronary artery disease or cardiac transplant vasculopathy defined as coronary artery stenosis(narrowing) ranging from 30 to 70 percent by coronary angiography. Measured in this study as change in IVUS-assessed Plaque Volume from baseline to one year.

  Baseline and 1 Year

Secondary Outcomes (5)

• Percentage of Participants With ≥20% Coronary Artery Diameter Reduction After Acetylcholine

  At Baseline and 1 Year

• ADMA Level at One Year Post Transplant

  1 year post Transplant

• The Percentage of Endothelial Progenitor Cells ( EPC) in Peripheral Blood in Patients One Year After Transplant

  at one year

• Fractional Flow Reserve (FFR) at One Year Post Transplant

  at one year post Transplant

• Index of Microcirculatory Resistance at One Year Post Heart Transplant

  one year

Study Arms (2)

ramipril

ACTIVE COMPARATOR

ramipril, 5mg starting dose to maximum dose of 20mg daily dose for one year.

Drug: ramipril

Placebo

PLACEBO COMPARATOR

Sugar pill manufactured to mimic ramipril 5mg starting dose , increasing to 20mg daily for one year.

Drug: Placebo

Interventions

ramipril DRUG

Use of a ACE ( angiotension converting enzyme) inhibitors post heart Transplant for Blood pressure control.

Also known as: Altace

ramipril

Placebo DRUG

Use of a placebo post heart Transplant for Blood pressure control.

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Heart transplant recipient within the first month of transplant;
• years of age or older;
• Must have a serum creatinine less than 2.0 mg/dl;
• Will provide written informed consent;
• Female patients of childbearing potential must have negative pregnancy test;
• For pediatric patient, parent(s) will provide consent and the child will sign assent.

You may not qualify if:

• Less than 12 years of age;
• Have more than one solid organ transplant at time of heart transplant;
• Has serum creatinine greater than 2.0 mg/dl;
• Pregnancy.

Sponsors & Collaborators

• Stanford University: lead
• VA Palo Alto Health Care System: collaborator
• Cedars-Sinai Medical Center: collaborator

Study Sites (2)

VA Palo Alto Health Care System

Palo Alto, California, 94304, United States

Location

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (3)

• Arashi H, Sato T, Kobashigawa J, Luikart H, Kobayashi Y, Okada K, Sinha S, Honda Y, Yeung AC, Khush K, Fearon WF. Long-term clinical outcomes with use of an angiotensin-converting enzyme inhibitor early after heart transplantation. Am Heart J. 2020 Apr;222:30-37. doi: 10.1016/j.ahj.2020.01.003. Epub 2020 Jan 9.

  PMID: 32007823 DERIVED

• Fearon WF, Okada K, Kobashigawa JA, Kobayashi Y, Luikart H, Sana S, Daun T, Chmura SA, Sinha S, Cohen G, Honda Y, Pham M, Lewis DB, Bernstein D, Yeung AC, Valantine HA, Khush K. Angiotensin-Converting Enzyme Inhibition Early After Heart Transplantation. J Am Coll Cardiol. 2017 Jun 13;69(23):2832-2841. doi: 10.1016/j.jacc.2017.03.598.

  PMID: 28595700 DERIVED

• Lee JH, Okada K, Khush K, Kobayashi Y, Sinha S, Luikart H, Valantine H, Yeung AC, Honda Y, Fearon WF. Coronary Endothelial Dysfunction and the Index of Microcirculatory Resistance as a Marker of Subsequent Development of Cardiac Allograft Vasculopathy. Circulation. 2017 Mar 14;135(11):1093-1095. doi: 10.1161/CIRCULATIONAHA.116.025268. No abstract available.

  PMID: 28289008 DERIVED

MeSH Terms

Interventions

Ramipril

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: William F. Fearon, M.D.
• Organization: Stanford University

wfearon@stanford.edu

650 725-2621

Study Officials

• William F Fearon

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: February 26, 2010
• First Posted: March 2, 2010
• Study Start: June 1, 2009
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: January 26, 2017
• Results First Posted: July 27, 2016

Record last verified: 2016-12

Locations

US (2)