Lipoprotein-associated Phospholipase A2 (Lp-PLA2) Progenitor Cells and Coronary Atherosclerosis in Humans

NCT01067339 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: 10-0000445R01HL0929545R01AG031750
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

AIM III is a prospective, randomized, double-blinded, placebo controlled trial. The study is directly connected to IRB 08-008161 as a specific aim of the National Institute of Health (NIH) grant. Participants may either consent to and qualify for AIM I and AIM II (IRB 08-008161) or have a cardiac catheterization with acetylcholine testing in the Cardiac Catheterization Laboratory at Mayo Clinic in Rochester, Minnesota to be considered for this study.

Conditions

Endothelial Dysfunction

Keywords

coronary endothelial dysfunction; coronary vasospasm

Outcome Measures

Primary Outcomes (2)

• Percentage Change in Coronary Artery Diameter

  The change of coronary artery diameter was measured in response to a maximal dose of acetylcholine administered intracoronary during an invasive coronary endothelial function assessment. Percentage change in coronary artery diameter provides a measure of endothelium dependent epicardial function.

  baseline, six months

• Percentage Change in Coronary Blood Flow (CBF)

  The change in coronary blood flow was measured in response to maximal dose of acetylcholine administered intracoronary during an invasive coronary endothelial function assessment. Percentage change in coronary blood flow provides a measure of endothelium dependent microvascular function.

  baseline, six months

Study Arms (2)

Darapladib

EXPERIMENTAL

Subjects randomized to this arm will receive a darapladib tablet, 160 mg, by mouth, once per day for 6 months.

Drug: darapladib

Placebo

PLACEBO COMPARATOR

Subjects randomized to this arm will receive a placebo tablet matching the study drug, once per day for 6 months.

Drug: placebo

Interventions

darapladib DRUG

darapladib, tablet, 160 mg, by mouth, one time daily, 6 month duration

Darapladib

placebo DRUG

placebo, by mouth, once daily for six months

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients undergoing coronary angiography including endothelial function testing with the medication acetylcholine in the cardiac catheterization laboratory at Mayo Clinic. Patients may be enrolled in AIM I and AIM II IRB 08-008161 :Lp-PLA2, Progenitor Cells and Atherosclerosis in Humans".
• Male or female aged at least 18 years, inclusive, at screening. Female subjects must be post-menopausal or using a highly effective method for avoidance of pregnancy. The decision to include or exclude women of childbearing potential may be made at the discretion of the investigator in accordance with local practice in relation to adequate contraception.
• Age greater than 18 up to age 85

You may not qualify if:

• Current severe heart failure New York Heart Association class III or IV with ejection fraction less than 40%
• Unstable angina
• Myocardial infarction or angioplasty within 6 months prior to entry into the study
• Planned coronary revascularization (PCI or CABG)
• Planned major surgical procedure
• Patients with segments with endothelial dysfunction of less than 10 mm in length or complete occlusion will be excluded.
• Current liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) or evidence of abnormal liver function tests (total bilirubin or alkaline phosphatase \> 1.5 x upper limit of normal (UNL); or alanine transaminase (ALT) or aspartate amino transferase (AST) \> 2.5 x UNL or other hepatic abnormalities that in the opinion of the investigator would preclude the subject from participation in the study.
• Chronic or acute kidney disease with serum creatinine greater than or equal to 2 mg/dL or estimated glomerular filtration rate \<40 mL/min/1.73m2, renal transplant status, history of contrast nephropathy,
• Poorly controlled hypertension despite lifestyle modifications and pharmacotherapy. (systolic BP \>160 mm Hg and/or diastolic BP \>110 mm Hg),
• Poorly controlled diabetes mellitus (HbA1c \>10%),
• Current or within 1 month use of any form of corticosteroids,
• Severe asthma that is poorly controlled on pharmacotherapy
• History of anaphylaxis, anaphylactoid (resembling anaphylaxis) reactions
• Current life-threatening conditions other than vascular disease, alcohol or drug abuse within the last 6 months
• Malignancy within the past 5 years,

Sponsors & Collaborators

• Mayo Clinic: lead
• GlaxoSmithKline: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Prasad M, Lennon R, Barsness GW, Prasad A, Gulati R, Lerman LO, Lerman A. Chronic inhibition of lipoprotein-associated phospholipase A2 does not improve coronary endothelial function: A prospective, randomized-controlled trial. Int J Cardiol. 2018 Feb 15;253:7-13. doi: 10.1016/j.ijcard.2017.09.171.

  PMID: 29306475 DERIVED

MeSH Terms

Conditions

Coronary Vasospasm

Interventions

darapladib

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Results Point of Contact

• Title: Amir Lerman, MD
• Organization: Mayo Clinic

lerman.amir@mayo.edu

507-284-6429

Study Officials

• Amir Lerman, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: February 9, 2010
• First Posted: February 11, 2010
• Study Start: February 4, 2010
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: April 18, 2017
• Results First Posted: March 15, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)