Cardiovascular Diseases, Diabetes
Conditions
Keywords
cardiovascular, alcohol, diabetes
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.
Interventions
OTHERAlcohol
\ 15 gm daily of beer, wine, or spirits for \ 6 years
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Harvard School of Public Health (HSPH)
Wake Forest University Health Sciences
Julius Center
Beth Israel Deaconess Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Masking description
Clinical outcome events will be assessed through medical record review by a masked Medical Safety Officer (MSO).
Intervention model description
Balanced-design randomized trial, comparing the effects of one standard serving (\ 15 grams) of alcohol intake daily to abstention.
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
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: 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Pre-Diabetes | Every 12 months for 90 months or closeout | Progression among normoglycemic individuals to ADA-defined pre-diabetes. |
| 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). |
| Cardiovascular Death | Every 3 months for 90 months or closeout, or date of death | Time from baseline to cardiovascular mortality. |
Countries
Netherlands, Nigeria, United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Alcohol One standard serving of alcohol (\
15 gm) daily
Alcohol: \
15 gm daily of beer, wine, or spirits for \
6 years | 15 |
| Abstention Abstention from alcohol | 17 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study ended by NIH | 15 | 17 |
Baseline characteristics
| Characteristic | Alcohol | Abstention | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 14 Participants | 10 Participants | 24 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 7 Participants | 8 Participants |
| Age, Continuous | 73.5 Years STANDARD_DEVIATION 8.7 | 68.5 Years STANDARD_DEVIATION 10.3 | 70.8 Years STANDARD_DEVIATION 9.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 17 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 10 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 7 Participants | 15 Participants |
| Region of Enrollment Netherlands | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Nigeria | 4 participants | 5 participants | 9 participants |
| Region of Enrollment United States | 11 participants | 11 participants | 22 participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Male | 8 Participants | 10 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 17 |
| other Total, other adverse events | 0 / 15 | 0 / 17 |
| serious Total, serious adverse events | 0 / 15 | 0 / 17 |
Outcome results
Primary
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.
Time frame: Every 3 months for up to 90 months or close out, or until date of death
Population: 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.
Secondary
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.
Time frame: Every 3 months for up to 90 months or close out, or until date of death
Population: 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.
Secondary
Diabetes
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
Population: 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.
Other Pre-specified
Cardiovascular Death
Time from baseline to cardiovascular mortality.
Time frame: Every 3 months for 90 months or closeout, or date of death
Population: 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.
Other Pre-specified
Components of Primary Composite Endpoint
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
Population: 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.
Other Pre-specified
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.
Time frame: Every 3 months for 90 month or close out, or until date of death
Population: 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.
Other Pre-specified
Pre-Diabetes
Progression among normoglycemic individuals to ADA-defined pre-diabetes.
Time frame: Every 12 months for 90 months or closeout
Population: 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.