Statin and Angiotensin-converting Enzyme Inhibitor on Symptoms in Patients With SCAD (SAFER-SCAD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Cardiology Research UBC
Sponsor:
Information provided by (Responsible Party):
Dr. Tara Sedlak, Cardiology Research UBC
ClinicalTrials.gov Identifier:
NCT02008786
First received: December 7, 2013
Last updated: July 23, 2014
Last verified: July 2014
  Purpose

An emerging cause of heart attack in young women is a dissection (or tear) in the coronary arteries. Many of these young women continue to have chest pain long after the tear has healed and this is thought to be due to problems with their small blood vessels of the heart (or microcirculation). We want to determine whether commonly used medications for coronary artery disease including statins (for cholesterol) and angiotensin-converting enzyme inhibitors (for blood pressure) reduce chest pain and improve small vessel function in these patients.


Condition Intervention Phase
Coronary Artery Dissection, Spontaneous
Drug: ramipril
Drug: rosuvastatin
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effects of Statin and Angiotensin-converting Enzyme Inhibitor on Coronary Flow Reserve, indEx of Microcirculatory Resistance, and Symptoms in Patients With Spontaneous Coronary Artery Dissection (SAFER-SCAD) Study

Resource links provided by NLM:


Further study details as provided by Cardiology Research UBC:

Primary Outcome Measures:
  • Angina frequency domain of the SAQ [ Time Frame: 16 weeks after each intervention ] [ Designated as safety issue: No ]
    Angina frequency domain of the SAQ, collected at baseline and after each intervention to assess angina frequency change over time. We hypothesize that mean SAQ will improve by at least 20 points in each treatment group compared to placebo.


Secondary Outcome Measures:
  • Acute coronary syndrome or hospitalization for angina [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    As a secondary objective, to evaluate whether ACEI or statin versus placebo reduces the combined endpoint of acute coronary syndrome (ACS) or hospitalization for angina at 52 weeks


Estimated Enrollment: 40
Study Start Date: June 2014
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rosuvastatin, placebo
rosuvastatin 10-20mg daily or placebo (suggested dose of 10mg for Asians, and 20mg for others)
Drug: rosuvastatin
10-20mg (suggested dose 10mg for Asians, 20mg for everyone else)
Other Name: crestor
Drug: placebo
Experimental: Ramipril, placebo
ramipril (starting dose of ramipril at 5mg daily titrating up to 10mg daily at 1 week if tolerated) versus placebo
Drug: ramipril
5-10mg (starting dose 5mg titrating up to 10mg if tolerated after 1 week)
Other Name: Altace
Drug: placebo

Detailed Description:

In patients with spontaneous coronary artery dissection (SCAD), many continue to have ongoing signs and symptoms of ischemia after the dissection has healed. Further, 1 in 5 women will experience recurrent SCAD in long-term follow-up. To date, no study has investigated the pathophysiologic mechanism behind ongoing symptoms or recurrence of SCAD, but microvascular coronary dysfunction (MCD) has been suggested. Coronary reactivity testing (CRT) is an invasive procedure currently being done in MCD patients as the gold standard technique. In particular, a coronary flow reserve (CFR) < 2.5 has been shown to be both diagnostic of the condition and prognostic of a 2 fold increased risk of cardiac events. Please see below for a detailed description of CRT. In brief, a dual temperature and pressure sensor tipped wire by Radi Medical Systems (St Jude Medical, St Paul, MN) will be placed into the dissected and non-dissected coronary arteries of the patient. This will measure CFR by thermodilution and will also allow the measurement of the index of microcirculatory resistance (IMR). IMR has been found to correlate well with true microvascular resistance.

In addition to a lack of diagnostic strategies, there is a paucity of research into therapeutic strategies. Most women are conservatively managed with medications, however, there is no consensus as to which pharmacologic therapies should be used. Case reports have suggested benefit with antiplatelet agents (e.g. aspirin) and beta-blockers (reduction of arterial wall shear stress). To date no study has investigated the effects of statins or Angiotensin Converting Enzyme Inhibitors (ACEIs) in SCAD patients. Both agents have been studied in the MCD population and been found to reduce angina frequency and improve CFR after 16 weeks.

Purpose:

To measuring the CFR and IMR in 40 SCAD patients with ongoing chest pain who are at least 3 months from their dissection to determine the proportion with microvascular dysfunction and to investigate prospectively whether the addition of an ACEI or a statin to usual care in patients with ongoing chest pain and a CFR <3.0 improves chest pain frequency by Seattle Angina Questionnaire (SAQ) at 16 weeks compared to placebo.

Hypothesis:

We hypothesize that the average CFR in patients at least 3 months out from their SCAD will be <2.5 and that their IMR will be abnormal. Further, we hypothesize that the addition of either an ACEI and/or statin will improve chest pain frequency by at least 20 points on the SAQ at 16 weeks compared to placebo.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Any woman with prior SCAD who is at least 3 months out from her SCAD and has ongoing symptoms of chest pain.
  • Females of child-bearing age must have a negative pregnancy test at enrollment
  • Coronary Flow Reserve(CFR) < 3.0

Exclusion Criteria:

  • Renal dysfunction with Glomerular Filtration Rate <50 ml/min
  • Patients not willing to undergo coronary angiography
  • Patients with a prior intolerance or allergy to rosuvastatin or ramipril
  • Inability to perform CRT or CFR >3.0
  • Obstructive coronary artery disease (stenosis >50% in any artery) or residual dissection >50% with distal flow abnormalities
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02008786

Contacts
Contact: Tara L Sedlak, MD 604-875-5487 Tara.Sedlak@vch.ca

Locations
Canada, British Columbia
Vancouver General Hospital Recruiting
Vancouver, British Columbia, Canada, V5Z 1M9
Contact: Tara L Sedlak, MD    604-875-5487    Tara.Sedlak@vch.ca   
Principal Investigator: Jacqueline Saw, MD         
Principal Investigator: Tara Sedlak, MD         
Sponsors and Collaborators
Cardiology Research UBC
  More Information

No publications provided

Responsible Party: Dr. Tara Sedlak, Cardiologist, Cardiology Research UBC
ClinicalTrials.gov Identifier: NCT02008786     History of Changes
Other Study ID Numbers: SAFER-SCAD
Study First Received: December 7, 2013
Last Updated: July 23, 2014
Health Authority: Canada: Ethics Review Committee

Keywords provided by Cardiology Research UBC:
Coronary Artery Dissection, Spontaneous
Angina

Additional relevant MeSH terms:
Aneurysm, Dissecting
Aneurysm
Vascular Diseases
Cardiovascular Diseases
Rosuvastatin
Enzyme Inhibitors
Ramipril
Angiotensin-Converting Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Protease Inhibitors
Antihypertensive Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on September 29, 2014