MACH15: Moderate Alcohol and Cardiovascular Health Trial

• Sponsor: Beth Israel Deaconess Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03169530
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH), Harvard School of Public Health (HSPH) (Other), Wake Forest University Health Sciences (Other), Julius Center (Other)
• Enrollment: 103
• Locations: 4
• Arms: 2
• Actual Duration (Months): 4.3
• Patients Per Site: 25.8
• Patients Per Site Per Month: 6

Study Details

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	N/A

Study Design

• Study Type: Interventional
• 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.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: Feb 5, 2018
• Actual Primary Completion Date: Jun 15, 2018
• Actual Study Completion Date: Jun 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 Names: ethanol, beer, wine, spirits
No Intervention: Abstention Abstention from alcohol

Outcome Measures

Primary Outcome Measures

1. Cardiovascular Disease or Death [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 [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 [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 [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 [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 [Every 3 months for 90 months or closeout, or date of death]

   Time from baseline to cardiovascular mortality.

4. Pre-Diabetes [Every 12 months for 90 months or closeout]

   Progression among normoglycemic individuals to ADA-defined pre-diabetes.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

3. Previous myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), carotid endarterectomy (CE), carotid stenting;

4. Peripheral artery disease (PAD) with revascularization;

5. Acute coronary syndrome with or without resting electrocardiogram (ECG) change, ECG changes on a graded exercise test (GXT), or positive cardiac imaging study;

6. Prior stroke documented on brain imaging or with a persistent deficit.

7. Subclinical CVD, confirmed in available medical records:

8. At least a 50% diameter stenosis of a coronary, carotid, or lower extremity artery;

9. Coronary artery calcium score ≥400 Agatston units;

10. Ankle brachial index (ABI) ≤0.90;

11. Left ventricular hypertrophy (LVH) by ECG (based on computer reading), echocardiogram report, or other cardiac imaging procedure report;

12. 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

	Site	City	State	Country	Postal Code
1	Johns Hopkins ProHealth Clinical Research Center	Baltimore	Maryland	United States	21207
2	Wake Forest Sticht Center on Aging	Winston-Salem	North Carolina	United States	27157
3	Julius Clinical	Zeist		Netherlands
4	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)

• Study Protocol and Statistical Analysis Plan - Apr 6, 2018
• Informed Consent Form - Apr 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. Review.

• Responsible Party: Kenneth Mukamal, Principal Investigator, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT03169530
• Other Study ID Numbers: 2017P000333; U10AA025286
• First Posted: May 30, 2017
• Last Update Posted: Mar 15, 2019
• Last Verified: Feb 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Kenneth Mukamal, Principal Investigator, Beth Israel Deaconess Medical Center: cardiovascular, alcohol, diabetes
• Additional relevant MeSH terms: Cardiovascular Diseases; Ethanol

Study Results

Participant Flow

Recruitment Details	103 subjects provided signed consent, 32 subjects were randomized. The additional 71 subjects were in the screening or in the run-in stage of the trial at the time of study cessation.
Pre-assignment Detail	103 subjects provided signed consent, 32 subjects were randomized. The additional 71 subjects were in the screening or run-in stages of the trial at the time of study cessation.

Arm/Group Title	Alcohol	Abstention
Arm/Group Description	One standard serving of alcohol (~15 gm) daily Alcohol: ~15 gm daily of beer, wine, or spirits for ~6 years	Abstention from alcohol
Period Title: Overall Study
STARTED	15	17
COMPLETED	0	0
NOT COMPLETED	15	17

Baseline Characteristics

Arm/Group Title	Alcohol	Abstention	Total
Arm/Group Description	One standard serving of alcohol (~15 gm) daily Alcohol: ~15 gm daily of beer, wine, or spirits for ~6 years	Abstention from alcohol	Total of all reporting groups
Overall Participants	15	17	32
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	1 6.7%	7 41.2%	8 25%
>=65 years	14 93.3%	10 58.8%	24 75%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	73.5 (8.7)	68.5 (10.3)	70.8 (9.8)
Sex: Female, Male (Count of Participants)
Female	7 46.7%	7 41.2%	14 43.8%
Male	8 53.3%	10 58.8%	18 56.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	15 100%	17 100%	32 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	6 40%	10 58.8%	16 50%
White	8 53.3%	7 41.2%	15 46.9%
More than one race	1 6.7%	0 0%	1 3.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Netherlands	0 0%	1 5.9%	1 3.1%
United States	11 73.3%	11 64.7%	22 68.8%
Nigeria	4 26.7%	5 29.4%	9 28.1%

Outcome Measures

1. Primary Outcome

Title	Cardiovascular Disease or Death
Description	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.
Time Frame	Every 3 months for up to 90 months or close out, or until date of death

Outcome Measure Data

Analysis Population Description

The trial was closed prior to any subject competing a 3-month visit, precluding assessment of the primary outcome. Therefore, no data for the CV disease outcome were collected or analyzed prior to study termination. No subjects died during the trial.

Arm/Group Title	Alcohol	Abstention
Arm/Group Description	One standard serving of alcohol (~15 gm) daily Alcohol: ~15 gm daily of beer, wine, or spirits for ~6 years	Abstention from alcohol
Measure Participants	0	0

2. Secondary Outcome

Title	Cardiovascular Disease
Description	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.
Time Frame	Every 3 months for up to 90 months or close out, or until date of death

Outcome Measure Data

Analysis Population Description

The trial was closed prior to any subject competing a 3-month visit, precluding assessment of this secondary outcome. Therefore, no data for this outcome were collected or analyzed prior to study termination. No subjects died during the trial.

Arm/Group Title	Alcohol	Abstention
Arm/Group Description	One standard serving of alcohol (~15 gm) daily Alcohol: ~15 gm daily of beer, wine, or spirits for ~6 years	Abstention from alcohol
Measure Participants	0	0

3. Secondary Outcome

Title	Diabetes
Description	Progression among normoglycemic and pre-diabetes individuals to American Diabetes Association (ADA)-defined diabetes.
Time Frame	Every 12 months for 90 months or close out, or until date of first documented occurence

Outcome Measure Data

Analysis Population Description

The trial was closed prior to any subject competing a 12-month visit, precluding assessment of this outcome. Therefore, no data for the diabetes outcome were collected or analyzed prior to study termination.

Arm/Group Title	Alcohol	Abstention
Arm/Group Description	One standard serving of alcohol (~15 gm) daily Alcohol: ~15 gm daily of beer, wine, or spirits for ~6 years	Abstention from alcohol
Measure Participants	0	0

4. Other Pre-specified Outcome

Title	Hard Cardiovascular Disease or Death
Description	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.
Time Frame	Every 3 months for 90 month or close out, or until date of death

Outcome Measure Data

Analysis Population Description

The trial was closed prior to any subject competing a 3-month visit, precluding assessment of this outcome. Therefore, no data for this outcome were collected or analyzed prior to study termination. No subjects died during the trial.

Arm/Group Title	Alcohol	Abstention
Arm/Group Description	One standard serving of alcohol (~15 gm) daily Alcohol: ~15 gm daily of beer, wine, or spirits for ~6 years	Abstention from alcohol
Measure Participants	0	0

5. Other Pre-specified Outcome

Title	Components of Primary Composite Endpoint
Description	Time from baseline to the first occurrence of each of the components of primary outcome (5 outcomes).
Time Frame	Every 3 months for up to 90 months or close out, or until date of death

Outcome Measure Data

Analysis Population Description

The trial was closed prior to any subject competing a 3-month visit, precluding assessment of these outcomes. Therefore, no data were collected or analyzed prior to study termination. No subjects died during the trial.

Arm/Group Title	Alcohol	Abstention
Arm/Group Description	One standard serving of alcohol (~15 gm) daily Alcohol: ~15 gm daily of beer, wine, or spirits for ~6 years	Abstention from alcohol
Measure Participants	0	0

6. Other Pre-specified Outcome

Title	Cardiovascular Death
Description	Time from baseline to cardiovascular mortality.
Time Frame	Every 3 months for 90 months or closeout, or date of death

Outcome Measure Data

Analysis Population Description

The trial was closed prior to any subject competing a 3-month visit, precluding assessment of this outcome. Therefore, no data for this outcome were collected or analyzed prior to study termination. No subjects died prior to completion of a 3-month visit.

Arm/Group Title	Alcohol	Abstention
Arm/Group Description	One standard serving of alcohol (~15 gm) daily Alcohol: ~15 gm daily of beer, wine, or spirits for ~6 years	Abstention from alcohol
Measure Participants	0	0

7. Other Pre-specified Outcome

Title	Pre-Diabetes
Description	Progression among normoglycemic individuals to ADA-defined pre-diabetes.
Time Frame	Every 12 months for 90 months or closeout

Outcome Measure Data

Analysis Population Description

The trial was closed prior to any subject competing a 12-month visit, precluding assessment of this outcome. Therefore, no data for this outcome were collected or analyzed prior to study termination.

Arm/Group Title	Alcohol	Abstention
Arm/Group Description	One standard serving of alcohol (~15 gm) daily Alcohol: ~15 gm daily of beer, wine, or spirits for ~6 years	Abstention from alcohol
Measure Participants	0	0

Adverse Events

Time Frame	5 months; from first enrolled subject until study termination.
Arm/Group Title	Alcohol		Abstention
Arm/Group Description	One standard serving of alcohol (~15 gm) daily Alcohol: ~15 gm daily of beer, wine, or spirits for ~6 years		Abstention from alcohol
All Cause Mortality
	Alcohol		Abstention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/17 (0%)
Serious Adverse Events
	Alcohol		Abstention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Alcohol		Abstention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/17 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.