Statins and Endothelial Function in Patients With Coarctation of the Aorta

NCT00767572 | Terminated Phase 4 Results DMC

• 1 other identifier: H7151-32792-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Coarctation of the aorta (CoA) accounts for approximately 8% of all congenital heart problems. Patients with CoA are well known to have an increased rates of early heart disease, high blood pressure, heart failure and stroke. Abnormal arterial function (dilation and constriction of the blood vessels) has been observed in these patients and likely contributes to the increased risk of cardiovascular problems. However, therapies targeted at improving arterial function have not been investigated in this population. Statin therapy (cholesterol medicines like Lipitor) have been studied in other subgroups of patients with abnormal arterial function and has shown benefit in improving arterial function and reducing risk of cardiovascular problems. The investigators hypothesize that patients with CoA have abnormal arterial function leading to increased cardiovascular risk. We further hypothesize that statin therapy may improve this problem. We plan to compile a complete database of information regarding these patients cardiovascular health and propose to then examine the effect of atorvastatin (Lipitor) on arterial function as measured by changes in arm arterial function tests.

Conditions

Coarctation of the Aorta

Keywords

Coarctation of the aorta; cross over design; atorvastatin; endothelial function

Outcome Measures

Primary Outcomes (1)

• Pre-post Change in Brachial Artery Reactivity

  Brachial artery reactivity was assessed by Flow-mediated dilatation (FMD), performed before and after the 12 week period on therapy. FMD uses high-frequency ultrasound measurement of changes in brachial artery diameter after a 5-minute blood pressure cuff arterial occlusion. Brachial artery reactivity has been shown to predict long-term cardiovascular events.

  Baseline, 12 weeks

Study Arms (2)

atorvastatin

EXPERIMENTAL

Patients are randomized to either atorvastatin or placebo once daily for 12 weeks. There is a 4 week washout, and then the groups are switched for 12 weeks. Brachial artery assessment will be performed before and after each 12 week period on therapy.

Drug: atorvastatin

sugar pill

PLACEBO COMPARATOR

See above. Patients will be randomized to atorvastatin vs. placebo for 12 weeks and after a 4 week washout period the groups will be switched.

Drug: Sugar pill

Interventions

atorvastatin DRUG

Atorvastatin 80mg daily vs. placebo daily X 12 weeks, then 4 week washout period, then cross over groups to complete another 12 weeks. (Total study time is 28 weeks (12+4+12)

Also known as: Lipitor

atorvastatin

Sugar pill DRUG

atorvastatin 80mg daily vs. placebo daily X 12 weeks, then 4 week washout, then cross over groups X 12 weeks. Total study time is 28weeks (12+4+12).

Also known as: placebo

sugar pill

Eligibility Criteria

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

You may qualify if:

• patients over the age of 18 years with repaired coarctation of the aorta (CoA) and willing to participate in all portions of the study including follow up, blood draws, urine sample, echocardiogram, MRI, brachial artery flow-mediated dilatation (FMD) testing, Carotid Intima Media Thickness (CIMT) testing and statin administration.

You may not qualify if:

• patients who are pregnant, nursing, or planning on becoming pregnant in the subsequent year
• current smokers
• patients with documented coronary artery disease (CAD), other systemic inflammatory disorder such as systemic lupus erythematosis or rheumatoid arthritis
• patients already on statin therapy or who have had previous adverse effects to statin therapy
• patients with hepatic transaminases \>2X the upper limit of normal
• patients with creatinine clearance \<60mg/dL
• patients who have implanted devices such as pacemakers or defibrillators that preclude MRI testing
• patients with low blood pressure at baseline (\< 90/50)
• patients who are unwilling or unable to comply with the aforementioned portions of the study

Sponsors & Collaborators

• University of California, San Francisco: lead
• American Heart Association: collaborator

Study Sites (1)

UCSF Medical Center, 505 Parnassus Ave

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Aortic Coarctation

Interventions

Atorvastatin; Sugars

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Carbohydrates

Limitations and Caveats

All patients were enrolled and completed the study interventions and assessments. Technical problems with measurements may have led to some unreliable data.

Results Point of Contact

• Title: Dr. Doreen DeFaria Yeh
• Organization: UCSF

ddefariayeh@partners.org

617-643-7024

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2008
• First Posted: October 7, 2008
• Study Start: August 1, 2008
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: October 14, 2013
• Results First Posted: October 14, 2013

Record last verified: 2013-10

Locations

US (1)