Moderate Alcohol and Cardiovascular Health Trial (MACH15)

• ClinicalTrials.gov Identifier: NCT03169530
• Recruitment Status: Terminated
• First Posted: May 30, 2017
• Results First Posted: January 30, 2019
• Last Update Posted: March 15, 2019
• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA); Harvard School of Public Health (HSPH); Wake Forest University Health Sciences; Julius Center
• Information provided by (Responsible Party): Kenneth Mukamal, Beth Israel Deaconess Medical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cardiovascular Diseases; Diabetes	Other: Alcohol	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 103 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Balanced-design randomized trial, comparing the effects of one standard serving (~15 grams) of alcohol intake daily to abstention.
• Masking: Single (Outcomes Assessor)
• Masking Description: Clinical outcome events will be assessed through medical record review by a masked Medical Safety Officer (MSO).
• Primary Purpose: Prevention
• Official Title: Moderate Alcohol and Cardiovascular Health Trial
• Actual Study Start Date: February 5, 2018
• Actual Primary Completion Date: June 15, 2018
• Actual Study Completion Date: June 15, 2018

Arms and Interventions

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 Name: ethanol, beer, wine, spirits
No Intervention: Abstention; Abstention from alcohol

Outcome Measures

Primary Outcome Measures :

1. Cardiovascular Disease or Death [ Time Frame: Every 3 months for up to 90 months or close out, or until date of 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.

Secondary Outcome Measures :

1. Cardiovascular Disease [ Time Frame: Every 3 months for up to 90 months or close out, or until date of 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 cardiovascular mortality.
2. Diabetes [ Time Frame: Every 12 months for 90 months or close out, or until date of first documented occurence ]
   Progression among normoglycemic and pre-diabetes individuals to American Diabetes Association (ADA)-defined diabetes.

Other Outcome Measures:

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Maryland

Johns Hopkins ProHealth Clinical Research Center

Baltimore, Maryland, United States, 21207

United States, North Carolina

Wake Forest Sticht Center on Aging

Winston-Salem, North Carolina, United States, 27157

Netherlands

Julius Clinical

Zeist, Netherlands

Nigeria

Center for Bioethics and Research

Ibadan, Nigeria, 200001

Sponsors and Collaborators

Beth Israel Deaconess Medical Center

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Harvard School of Public Health (HSPH)

Wake Forest University Health Sciences

Julius Center

Investigators

• Principal Investigator: Kenneth J Mukamal, MD; Beth Israel Deaconess Medical Center

  Study Documents (Full-Text)

Documents provided by Kenneth Mukamal, Beth Israel Deaconess Medical Center:

Study Protocol and Statistical Analysis Plan  [PDF] April 6, 2018

Informed Consent Form  [PDF] April 6, 2018

More Information

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.

• Responsible Party: Kenneth Mukamal, Principal Investigator, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT03169530
• Other Study ID Numbers: 2017P000333; U10AA025286 ( U.S. NIH Grant/Contract )
• First Posted: May 30, 2017
• Results First Posted: January 30, 2019
• Last Update Posted: March 15, 2019
• Last Verified: February 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Sponsor prohibits data sharing.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Kenneth Mukamal, Beth Israel Deaconess Medical Center:

cardiovascular, alcohol, diabetes

Additional relevant MeSH terms:

Cardiovascular Diseases; Ethanol; Anti-Infective Agents, Local; Anti-Infective Agents; Central Nervous System Depressants; Physiological Effects of Drugs