Clinical trial NCT03169530: Moderate Alcohol and Cardiovascular Health Trial
Official title: Moderate Alcohol and Cardiovascular Health Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Cardiovascular Diseases
Diabetes
Keywords: cardiovascular, alcohol, diabetes
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
name: Harvard School of Public Health (HSPH)
name: Wake Forest University Health Sciences
name: Julius Center
First posted: 2017-05-30
Enrollment: 103
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Balanced-design randomized trial, comparing the effects of one standard serving (\~15 grams) of alcohol intake daily to abstention.
Primary purpose: PREVENTION

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.


Eligibility 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.

Primary outcomes:
measure: Cardiovascular Disease or Death
timeFrame: Every 3 months for up to 90 months or close out, or until date of death
Secondary outcomes:
measure: Cardiovascular Disease
timeFrame: Every 3 months for up to 90 months or close out, or until date of death
measure: Diabetes
timeFrame: Every 12 months for 90 months or close out, or until date of first documented occurence
Other outcomes:
measure: Hard Cardiovascular Disease or Death
timeFrame: Every 3 months for 90 month or close out, or until date of death
measure: Components of Primary Composite Endpoint
timeFrame: Every 3 months for up to 90 months or close out, or until date of death
measure: Cardiovascular Death
timeFrame: Every 3 months for 90 months or closeout, or date of death
measure: Pre-Diabetes
timeFrame: Every 12 months for 90 months or closeout
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins ProHealth Clinical Research Center
state: Maryland
city: Winston-Salem
country: United States
facility: Wake Forest Sticht Center on Aging
state: North Carolina
city: Zeist
country: Netherlands
facility: Julius Clinical
city: Ibadan
country: Nigeria
facility: Center for Bioethics and Research
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Kenneth J Mukamal, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.