Endothelial DysfunctionPhase 3NCT01067339
Lipoprotein-associated Phospholipase A2 (Lp-PLA2) Progenitor Cells and Coronary Atherosclerosis in Humans
A Phase 3 study testing darapladib in people with Endothelial Dysfunction, run by Mayo Clinic at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Endothelial Dysfunction
- What is being tested?
- darapladib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Feb 2010to Nov 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 28Show fewer
- Angiographic exclusion criteria include left main disease with greater than 30% stenosis on angiogram, luminal diameter of the study vessel less than 2.5 mm, severe tortuousity of the study vessel, or any other relevant anatomical reasons that the investigator deems inappropriate for the study.
- 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,
- Positive pregnancy test (all female subjects of childbearing potential must have a urine β-human chorionic gonadotropin (hCG) pregnancy test performed at Screening and/or within 7 days prior to randomization) or is known to be pregnant or lactating.
- Current or planned chronic administration of strong oral or injectable cytochrome P-450 isoenzyme 3A4 (CYP3A4) inhibitors.
- Subjects with both parents of Japanese, Chinese, or Korean ancestry must have a blood sample collected for assessment of Lp-PLA2 activity by the central laboratory prior to randomization. Those with Lp-PLA2 activity ≤10 nmol/min/mL will be excluded from participation in the study.
- Previous exposure to darapladib (SB-480848).
- Use of an investigational device or investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of the study medication, or any subject the investigator deems unsuitable for the study
- Patients who require treatment with positive inotropic agents other than digoxin during the study
- Patients with cerebrovascular accident within 6 months prior to entry into the study
- Significant endocrine, hepatic or renal disorders
- Local or systemic infectious disease within 4 weeks prior to entry into study
- Mental instability
- Federal Medical Center inmates
- Hemoglobin less than 12 mg/dL
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Lp-PLA2, Progenitor Cells and Coronary Atherosclerosis in Humans AIM III
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.
Read the detailed description
The main goal of AIM III is to assess and quantify the effect of long-term administration of darapladib 160 mg once a day, a selective, reversible, orally active inhibitor of plasma and vascular Lp-PLA2, on coronary endothelial function, progression of coronary atherosclerosis as determined by intravascular ultrasound (IVUS), and atherosclerosis in patients with early atherosclerosis. Patients with evidence of coronary endothelial dysfunction, as determined by intracoronary administration of acetylcholine during angiography and IVUS, will be followed for 6 months during once daily dosing of darapladib. Coronary endothelial function is determined by the changes in coronary artery diameter and coronary blood flow response to the intracoronary administration of acetylcholine and adenosine. The patients will be followed in clinic 6 months. They will have follow-up angiography, assessment of endothelial function, and IVUS during the six month visit.
- Conditions
- Endothelial Dysfunction
- Being tested
- darapladib, placebo
- Keywords
- coronary endothelial dysfunction, coronary vasospasm
- Medical subject headings
- Coronary Vasospasm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
darapladibDrug
darapladib, tablet, 160 mg, by mouth, one time daily, 6 month duration
placeboDrug
placebo, by mouth, once daily for six months
| Study group | Role | What they receive |
|---|---|---|
| Darapladib | Experimental | Subjects randomized to this arm will receive a darapladib tablet, 160 mg, by mouth, once per day for 6 months. Receives: 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. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: baseline, six months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2010 (estimated)
- Study start4 Feb 2010
- Primary completionNov 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Endothelial DysfunctionStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline, National Heart, Lung, and Blood Institute (NHLBI), National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Amir Lerman, Mayo Clinic
- Investigators
- Amir Lerman, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01067339
- Sponsor's protocol ID
- 10-000044
- Other IDs
- 5R01HL092954, 5R01AG031750
- Status last verified
- Mar 2017
- First submitted
- 9 Feb 2010
- Last updated
- 18 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 29306475
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lp-PLA2, Progenitor Cells and Coronary Atherosclerosis in Humans AIM III
- ClinicalTrials.gov ID
- NCT01067339
- Acronym / sponsor ID
- 10-000044
- Conditions
- Endothelial Dysfunction
- Keywords
- coronary endothelial dysfunction, coronary vasospasm
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- GlaxoSmithKline, National Heart, Lung, and Blood Institute (NHLBI), National Institute on Aging (NIA)
- Study start
- 4 Feb 2010
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 11 Feb 2010 (estimated)
- Results
- Posted 15 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The main goal of AIM III is to assess and quantify the effect of long-term administration of darapladib 160 mg once a day, a selective, reversible, orally active inhibitor of plasma and vascular Lp-PLA2, on coronary endothelial function, progression of coronary atherosclerosis as determined by intravascular ultrasound (IVUS), and atherosclerosis in patients with early atherosclerosis. Patients with evidence of coronary endothelial dysfunction, as determined by intracoronary administration of acetylcholine during angiography and IVUS, will be followed for 6 months during once daily dosing of darapladib. Coronary endothelial function is determined by the changes in coronary artery diameter and coronary blood flow response to the intracoronary administration of acetylcholine and adenosine. The patients will be followed in clinic 6 months. They will have follow-up angiography, assessment of endothelial function, and IVUS during the six month visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Darapladib | Experimental | Drug: darapladibSubjects randomized to this arm will receive a darapladib tablet, 160 mg, by mouth, once per day for 6 months. |
| Placebo | Placebo comparator | Drug: placeboSubjects randomized to this arm will receive a placebo tablet matching the study drug, once per day for 6 months. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (28 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| darapladibdarapladib, tablet, 160 mg, by mouth, one time daily, 6 month duration | Drug | Darapladib |
| placeboplacebo, by mouth, once daily for six months | Drug | Placebo |
Primary outcome
Percentage Change in Coronary Artery Diameter
Time frame: baseline, six months
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.
Percentage Change in Coronary Blood Flow (CBF)
Time frame: baseline, six months
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29306475Prasad 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amir Lerman, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing darapladib in people with Endothelial Dysfunction, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage Change in Coronary Artery Diameter (time frame: baseline, six months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01067339, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2017.