Moderate Alcohol and Cardiovascular Health Trial (MACH15)

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.

Study Overview

• Status: Terminated
• Conditions: Cardiovascular Diseases; Diabetes
• Intervention / Treatment: Other: Alcohol

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Zeist, Netherlands
    • Julius Clinical
• Nigeria
  • Ibadan, Nigeria, 200001
    • Center for Bioethics and Research
• United States
  • Maryland
    • Baltimore, Maryland, United States, 21207
      • Johns Hopkins ProHealth Clinical Research Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Sticht Center on Aging

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  1. 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])

  2. Clinical CVD (more than 6 months prior to randomization), defined by:

     1. Previous myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), carotid endarterectomy (CE), carotid stenting;
     2. Peripheral artery disease (PAD) with revascularization;
     3. Acute coronary syndrome with or without resting electrocardiogram (ECG) change, ECG changes on a graded exercise test (GXT), or positive cardiac imaging study;
     4. Prior stroke documented on brain imaging or with a persistent deficit.

  3. Subclinical CVD, confirmed in available medical records:

     1. At least a 50% diameter stenosis of a coronary, carotid, or lower extremity artery;
     2. Coronary artery calcium score ≥400 Agatston units;
     3. Ankle brachial index (ABI) ≤0.90;
     4. Left ventricular hypertrophy (LVH) by ECG (based on computer reading), echocardiogram report, or other cardiac imaging procedure report;
     5. Abdominal aortic aneurysm (AAA) ≥5 cm with or without repair.

Exclusion Criteria:

• High alcohol consumption, defined by any one of the following:

  1. Alcohol Use Disorders Identification Test (AUDIT) score >5 at screening
  2. Drinking, on average, >7 alcoholic beverages/week during the past 6 months
  3. 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:

  1. moderate - severe psychiatric illness
  2. behavioral concerns regarding likelihood of low adherence to trial protocol
  3. a medical condition likely to limit survival to less than 3 years
  4. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Alcohol; One standard serving of alcohol (~15 gm) daily	Other: Alcohol; ~15 gm daily of beer, wine, or spirits for ~6 years; Other Names: ethanol, beer, wine, spirits
No Intervention: Abstention; Abstention from alcohol

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hard 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, or cardiovascular death.	Every 3 months for 90 month or close out, or until date of death
Components of Primary Composite Endpoint	Time from baseline to the first occurrence of each of the components of primary outcome (5 outcomes).	Every 3 months for up to 90 months or close out, or until date of death
Cardiovascular Death	Time from baseline to cardiovascular mortality.	Every 3 months for 90 months or closeout, or date of death
Pre-Diabetes	Progression among normoglycemic individuals to ADA-defined pre-diabetes.	Every 12 months for 90 months or closeout

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA); Wake Forest University Health Sciences; Harvard School of Public Health (HSPH); Julius Center
• Investigators: Principal Investigator: Kenneth J Mukamal, MD, Beth Israel Deaconess Medical Center

Publications and helpful links

General Publications

• Mukamal KJ, Clowry CM, Murray MM, Hendriks HF, Rimm EB, Sink KM, Adebamowo CA, Dragsted LO, Lapinski PS, Lazo M, Krystal JH. Moderate Alcohol Consumption and Chronic Disease: The Case for a Long-Term Trial. Alcohol Clin Exp Res. 2016 Nov;40(11):2283-2291. doi: 10.1111/acer.13231. Epub 2016 Sep 30.

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2018
• Primary Completion (Actual): June 15, 2018
• Study Completion (Actual): June 15, 2018

Study Registration Dates

• First Submitted: May 24, 2017
• First Submitted That Met QC Criteria: May 26, 2017
• First Posted (Actual): May 30, 2017

Study Record Updates

• Last Update Posted (Actual): March 15, 2019
• Last Update Submitted That Met QC Criteria: February 22, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: cardiovascular, alcohol, diabetes
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Central Nervous System Depressants; Ethanol
• Other Study ID Numbers: 2017P000333; U10AA025286 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Sponsor prohibits data sharing.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No