Moderate Alcohol and Cardiovascular Health Trial

Study Overview
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Brief Summary
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The Moderate Alcohol and Cardiovascular Health Trial (MACH15) is a multicenter, worldwide, randomized clinical trial of  15 gm of alcohol daily versus abstention, using a balanced parallel design and single-blind assessment of all outcomes among approximately 7,800 participants aged 50 years and older with advanced cardiovascular risk. Intervention will average 6 years in duration with a common close-out date. Following recruitment and pre-screening, participants will attend a screening visit followed by a two-week abstention washout period, a baseline visit and randomization, and subsequent visits at 3 months, 6 months, 12 months, and then annually until close-out.

Official Title
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Moderate Alcohol and Cardiovascular Health Trial

Conditions
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Cardiovascular Diseases, Diabetes

Intervention / Treatment
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* Other: Alcohol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥50 years at screening Postmenopausal, defined as 12 consecutive months without menstruation Not alcohol naïve, defined by having consumed at least one drink of alcohol in the past five years High risk for the occurrence of a new cardiovascular disease event, defined as having any one of the following: American Heart Association (AHA)/American College of Cardiology (ACC) Risk Score ≥15% within the past 24 months (among those without clinical or subclinical cardiovascular disease [CVD]) Clinical CVD (more than 6 months prior to randomization), defined by: Previous myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), carotid endarterectomy (CE), carotid stenting; Peripheral artery disease (PAD) with revascularization; Acute coronary syndrome with or without resting electrocardiogram (ECG) change, ECG changes on a graded exercise test (GXT), or positive cardiac imaging study; Prior stroke documented on brain imaging or with a persistent deficit. Subclinical CVD, confirmed in available medical records: At least a 50% diameter stenosis of a coronary, carotid, or lower extremity artery; Coronary artery calcium score ≥400 Agatston units; Ankle brachial index (ABI) ≤0.90; Left ventricular hypertrophy (LVH) by ECG (based on computer reading), echocardiogram report, or other cardiac imaging procedure report; Abdominal aortic aneurysm (AAA) ≥5 cm with or without repair. Exclusion Criteria: High alcohol consumption, defined by any one of the following: Alcohol Use Disorders Identification Test (AUDIT) score >5 at screening Drinking, on average, >7 alcoholic beverages/week during the past 6 months Drinking 6 or more alcoholic beverages on one occasion during the past 6 months Yale-Brown Obsessive Compulsive Scale-heavy drinking (Y-BOCS-hd) total score of ≥6 on questions 7, 8, and 10 Cardiovascular disease event (MI, revascularization procedure, or stroke) within the 6 months prior to randomization AHA Class III-IV heart failure History of alcohol or substance abuse (medical record confirmed or self-reported history) Other intolerance or allergy to alcohol Dual antiplatelet therapy History of gastric bypass surgery Any serious chronic liver disease (e.g., active hepatitis B and C infections) or liver tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT] and gamma-glutamyl transpeptidase [GGT]) >2 times the upper limit of the normal range using local standards Personal history of any colon or liver cancer Any other cancer with a life expectancy of less than 3 years Diagnosed with breast cancer that required either surgery or removal of breast tissue or chemotherapy Mother or sister ever diagnosed with breast cancer that required either surgery or removal of breast tissue or chemotherapy Estimated glomerular filtration rate (eGFR) <30 ml/min /1.73m2 or end-stage renal disease (ESRD) Ongoing use of any medication for which alcohol consumption is contraindicated A Patient Health Questionnaire (PHQ-9) ≥15 at screening History of any organ transplant Unintentional weight loss >10% in last 6 months Currently participating in another clinical trial (intervention trial) with CVD outcomes. Note: Participant must wait until the completion of his/her activities or the completion of the other trial before being screened for MACH15. Local restrictions for entry by participants can be more conservative if mandated. Not willing or able to provide a name and contact information for at least one additional contact person other than self Investigator discretion regarding appropriateness of participation or concern about intervention adherence, including: moderate - severe psychiatric illness behavioral concerns regarding likelihood of low adherence to trial protocol a medical condition likely to limit survival to less than 3 years advanced chronic disease, such as dementia, that requires 24-hour care Not willing or able to provide a signed and dated informed consent form Not willing or able to comply with all trial procedures.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Balanced-design randomized trial, comparing the effects of one standard serving ( 15 grams) of alcohol intake daily to abstention.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Alcohol<br>One standard serving of alcohol ( 15 gm) daily | Other: Alcohol<br>*  15 gm daily of beer, wine, or spirits for  6 years<br>* Other names: ethanol, beer, wine, spirits;|
| No Intervention: Abstention<br>Abstention from alcohol | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular Disease or Death | Time from baseline to a composite endpoint comprised of the first occurrence of a non-fatal myocardial infarction, non-fatal ischemic stroke, hospitalization for angina, coronary/carotid revascularization, or all-cause mortality. | Every 3 months for up to 90 months or close out, or until date of death | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular Disease | Time from baseline to a composite endpoint comprised of the first occurrence of a non-fatal myocardial infarction, non-fatal ischemic stroke, hospitalization for angina, coronary/carotid revascularization, or cardiovascular mortality. | Every 3 months for up to 90 months or close out, or until date of death | 
| Diabetes | Progression among normoglycemic and pre-diabetes individuals to American Diabetes Association (ADA)-defined diabetes. | Every 12 months for 90 months or close out, or until date of first documented occurence | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cardiovascular, alcohol, diabetes