Effect of ACE-Inhibition treatment on the function of the small vessels in the heart in Women with Assessed Vmall Vessel Dysfunction and No Obstructive Coronary Artery Disease.

Phase 1

• Conditions: Microvascular dysfunction/microvascular angina; MedDRA version: 18.0Level: LLTClassification code 10065566Term: Microvascular anginaSystem Organ Class: 100000004849; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2014-004490-17-DK
• Lead Sponsor: Bipebjerg University Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-10-29
• Last Update Posted: 8 August 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: Not specified

Inclusion Criteria

Patients from the iPower cohort with microvascular dysfunction defined as a TTDE measured CFR < 2.2 with a good quality (quality index > 3) examination who are normotensive will be included in the study. Patients with a CFR <2.0 will be invited before patients with a CFR between 2.0 - 2.2. Normotensive will in this study be defined as patients who have a blood pressure = 150 at last visit in iPower and who are not in treatment for documented hypertension. Patients will be found searching for patients in the iPower database with these criteria.

The iPower cohort has included women aged 18-80 with angina-like chest discomfort but no obstructive coronary artery disease (Coronary angiography with no significant stenotic lesions (<=50%) of epicardial vessels performed within 1 year of inclusion) since 2012.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 36
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 36

Exclusion Criteria

•Current treatment with ACE-inhibitors or Angiotensin II-antagonists
•Atrial fibrillation
•Pace-maker
•Allergy towards Ace-inhibitor, Ramipril ® or tool-medicine: Dipyridamole/adenosine, Nitro-glycerine or rescue medicine: Theophylline
•Baseline CFR >2.5 when entering ACIM-study.
•No episodes of chest pain within 6 months before inclusion
•Coronary angiography with significant stenotic lesions (>/=50%)
•Other cause of chest discomfort deemed highly likely
•Left ventricular ejection fraction below 45% assessed by echocardiography at baseline measurement
•Significant valvular heart disease (Definition: Verified in medical records after echocardiography. If the echocardiographer in this study suspects valvular heart disease, the patient is referred for expert evaluation and excluded from the study until valvular disease has been excluded. All definitions are taken from the guidelines of the Danish Society of Cardiology (DCS).
oHaemodynamic significant Aortic Stenosis: Valve area < 1 cm2 or <0.6 cm2/m2 body surface area.
oSevere aorta Regurgitation (AR): Vena contracta > 6 mm, Moderate/severe LV volume load, ERO > 0.3 cm².
oMitral Stenosis (MS): Valve area < 2.5 cm2.
oSevere Mitral Regurgitation (MR): ERO > 0.4 cm², Moderate/severe LV-load, Vena contracta > 6 mm.
•Congenital heart disease or cardiomyopathy verified in medical records
•Significant co-morbidity with < 1 year expected survival: decision made by the person responsible for inclusion based on the patient interview and/or medical records.
•Severe COPD with FEV1<50% of predicted
•Severe asthma defined as asthma which requires treatment with high dose inhaled corticosteroids (ICS) plus a second controller (long acting ß2 agonist (LABA), leukotriene modifier, theophylline or systemic corticosteroids) to prevent it from becoming uncontrolled or which remains uncontrolled despite this therapy.
•Previous verified myocardial infarction (Definition: verified in medical records, STEMI (ST segment elevation, elevated enzymes) or NSTEMI (elevated enzymes, ECG changes/no ECG changes).
•Previous revascularization (PCI or CABG)
•Elevated cardiac biomarkers: Troponin > 50 ng/l (high sensitive) or > 0.03 µg/l (4. generation), CKMB > 4.0 µg/l (women).
•ECG with verified ST-segment elevation
•Language- or other barrier to giving informed consent (for example mental ability to understand project)
•Travel distance: a distance to research hospital requiring more than 3 hours of travel
•Patient unwilling to participate (Low burden of symptoms, other illnesses, Lack of energy”, transport problems, anxiety because of the examination, other).
•No signed informed consent.
•Other (Pregnancy, significant psychiatric disorder)
•GFR < 50 mL/min/1,73 m2

WITHDRAWAL CRITERIA
Patients who will be withdrawn from participating in the study:
a)Suspected serious reaction where medication type will be unblinded by the sponsor by calling Glostrup pharmacy (open day and night)
b)If they do not want to continue with treatment before total up titration of treatment
c)Sustained side-effects which make the patients unable to take ACE-inhibitor/placebo before total up titration of treatment
d)Poor compliance defined as less than 70 % of the time not taking ACE-inhibitor/placebo assessed by investigator. Patients will also be excluded with a more than 2 months continuous pause from medication or more than 2 weeks continuous pause up to endpoint measurements.
e)Patients who do not

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified