Emulation of the Moderate Alcohol and Cardiovascular Health Trial (MACH15)

August 30, 2024 updated by: Goodarz Danaei, Harvard School of Public Health (HSPH)
The aim of this study is to assess how long-term alcohol consumption influences health risks by emulating the Moderate Alcohol and Cardiovascular Health Trial (MACH15). In the first step, the protocol of the emulation of MACH15, including eligibility criteria, alcohol regimens and assignment, follow-up, endpoints, causal contrasts of interest, and statistical analysis was specified. In the second step, the investigators will emulate an adapted version of MACH15 following the specified protocol using data from the UK Biobank.

Study Overview

Status

Completed

Conditions

Detailed Description

Observational data suggests that alcohol consumption lowers the risk of cardiovascular disease (CVD) compared to no consumption. Whether this relationship is truly causal remains uncertain because of the inherent limitations of observational studies, including unmeasured confounding and reverse causation. Mendelian randomization studies using genes as instrumental variables for alcohol are partially protected from these biases and have found no or harmful associations between alcohol consumption and CVD.

To date, there has only been one long-term randomized controlled trial to investigate the cardiovascular effects of alcohol consumption: the Moderate Alcohol and Cardiovascular Health Trial (MACH15; NCT Number: NCT03169530). It was, however, terminated shortly after initiation. An alternative to a real randomized trial like MACH15, which must first be completed and is subject to strict eligibility criteria to ensure safety, is to use observational data to emulate a (hypothetical) pragmatic randomized trial.

In this study, the investigators will emulate an adapted version of MACH15 using observational data from the UK Biobank, a large prospective cohort study of over 500,000 participants. The cardiometabolic effects of moderate drinking vs quitting, as originally planned in MACH15, as well as the effects of social and heavy/binge drinking on CVD, type 2 diabetes, other alcohol-related health outcomes, and death will be quantified.

Study Type

Observational

Enrollment (Actual)

503325

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

All people aged 40-69 years who were registered with the National Health Service and lived within 25 miles of one of the 22 study assessment centers in England, Wales, and Scotland were invited to participate. Overall, about 9.2 million invitations were mailed in order to recruit 503,325 participants (i.e. a response rate of 5.47%)

Description

Inclusion criteria:

  • 40-69 years old at enrollment
  • Currently drinking

Exclusion criteria:

  • Within the six months prior to baseline, cardiovascular disease event (myocardial infarction, revascularization procedure, or stroke)
  • Hospitalization due to heart failure
  • History of any of the following alcohol-related conditions, confirmed by a hospital record: alcoholic cardiomyopathy, alcoholic gastritis, alcoholic liver disease, degeneration of the nervous system due to alcohol, alcoholic myopathy, alcoholic polyneuropathy, alcohol-induced acute or chronic pancreatitis, alcohol use disorder; or self-reported history of alcoholic liver disease or alcohol use disorder
  • Dual antiplatelet therapy or coumarin anticoagulants
  • Serious chronic liver disease (active hepatitis B or C infection) in the past 6 months before baseline
  • Personal history of any colon or liver cancer
  • Personal history of breast cancer
  • Diagnosis of dementia
  • Not willing or able to provide a signed and dated informed consent form
  • Reduced alcohol compared to 10 years ago due to illness, ill health, or doctor's advice
  • Self-reported poor health

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiovascular disease or death
Time Frame: From date of baseline measurement until the date of first cardiovascular disease or death documented in hospital or death registry data, administrative censoring, or loss to follow-up, whichever came first, assessed up to 200 months
Composite endpoint comprised of the first occurrence of a non-fatal myocardial infarction, non-fatal ischemic stroke, hospitalization for angina, coronary/carotid revascularization, and all-cause mortality
From date of baseline measurement until the date of first cardiovascular disease or death documented in hospital or death registry data, administrative censoring, or loss to follow-up, whichever came first, assessed up to 200 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiovascular disease
Time Frame: From date of baseline measurement until the date of first cardiovascular disease documented in hospital or death registry data, administrative censoring, loss to follow-up, or death from other causes, whichever came first, assessed up to 200 months
Composite endpoint comprised of the first occurrence of a non-fatal myocardial infarction, non-fatal ischemic stroke, hospitalization for angina, coronary/carotid revascularization, and cardiovascular death
From date of baseline measurement until the date of first cardiovascular disease documented in hospital or death registry data, administrative censoring, loss to follow-up, or death from other causes, whichever came first, assessed up to 200 months
Type 2 diabetes
Time Frame: From date of baseline measurement until the date of first type 2 diabetes documented in hospital or death registry data, administrative censoring, loss to follow-up, or death from other causes, whichever came first, assessed up to 200 months
Progression among normoglycemic and pre-diabetes individuals to type 2 diabetes
From date of baseline measurement until the date of first type 2 diabetes documented in hospital or death registry data, administrative censoring, loss to follow-up, or death from other causes, whichever came first, assessed up to 200 months
Alcohol-related disease or death
Time Frame: From date of baseline measurement until the date of first alcohol-related disease or death documented in hospital, cancer, or death registry data, administrative censoring, or loss to follow-up, whichever came first, assessed up to 200 months
Composite endpoint comprised of the first occurrence of a non-fatal myocardial infarction, non-fatal ischemic stroke, heart failure, atrial fibrillation, cancer (except non-melanoma skin cancer), dementia, depression, infection with hospitalization, injury with hospitalization, liver cirrhosis, type 2 diabetes, and all-cause mortality
From date of baseline measurement until the date of first alcohol-related disease or death documented in hospital, cancer, or death registry data, administrative censoring, or loss to follow-up, whichever came first, assessed up to 200 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hard cardiovascular disease or death
Time Frame: From date of baseline measurement until the date of first hard cardiovascular disease or death documented in hospital or death registry data, admin. censoring, loss to follow-up, or death from other causes, whichever came first, assessed up to 200 months
Composite endpoint comprised of the first occurrence of a non-fatal myocardial infarction, non-fatal ischemic stroke, and cardiovascular death
From date of baseline measurement until the date of first hard cardiovascular disease or death documented in hospital or death registry data, admin. censoring, loss to follow-up, or death from other causes, whichever came first, assessed up to 200 months
Cardiovascular death
Time Frame: From date of baseline measurement until the date of cardiovascular death documented in death registry data, administrative censoring, loss to follow-up, or death from other causes, whichever came first, assessed up to 200 months
Cardiovascular death
From date of baseline measurement until the date of cardiovascular death documented in death registry data, administrative censoring, loss to follow-up, or death from other causes, whichever came first, assessed up to 200 months
Non-fatal myocardial infarction
Time Frame: From date of baseline measurement until the date of first non-fatal myocardial infarction documented in hospital data, administrative censoring, loss to follow-up, or death, whichever came first, assessed up to 200 months
First occurrence of a non-fatal myocardial infarction
From date of baseline measurement until the date of first non-fatal myocardial infarction documented in hospital data, administrative censoring, loss to follow-up, or death, whichever came first, assessed up to 200 months
Non-fatal ischemic stroke
Time Frame: From date of baseline measurement until the date of first non-fatal ischemic stroke documented in hospital data, administrative censoring, loss to follow-up, or death, whichever came first, assessed up to 200 months
First occurrence of a non-fatal ischemic stroke
From date of baseline measurement until the date of first non-fatal ischemic stroke documented in hospital data, administrative censoring, loss to follow-up, or death, whichever came first, assessed up to 200 months
Hospitalization for angina
Time Frame: From date of baseline measurement until the date of first hospitalization for angina documented in hospital data, administrative censoring, loss to follow-up, or death, whichever came first, assessed up to 200 months
First hospitalization for angina
From date of baseline measurement until the date of first hospitalization for angina documented in hospital data, administrative censoring, loss to follow-up, or death, whichever came first, assessed up to 200 months
Coronary/carotid revascularization
Time Frame: From date of baseline measurement until the date of first coronary/carotid revascularization documented in hospital data, administrative censoring, loss to follow-up, or death, whichever came first, assessed up to 200 months
First coronary/carotid revascularization
From date of baseline measurement until the date of first coronary/carotid revascularization documented in hospital data, administrative censoring, loss to follow-up, or death, whichever came first, assessed up to 200 months
All-cause mortality
Time Frame: From date of baseline measurement until the date of death documented in death registry data, administrative censoring, or loss to follow-up, whichever came first, assessed up to 200 months
Death
From date of baseline measurement until the date of death documented in death registry data, administrative censoring, or loss to follow-up, whichever came first, assessed up to 200 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Harvard School of Public Health (HSPH)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2006

Primary Completion (Actual)

November 30, 2022

Study Completion (Actual)

November 30, 2022

Study Registration Dates

First Submitted

August 28, 2024

First Submitted That Met QC Criteria

August 30, 2024

First Posted (Actual)

September 3, 2024

Study Record Updates

Last Update Posted (Actual)

September 3, 2024

Last Update Submitted That Met QC Criteria

August 30, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB23-1533

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Access to the UK Biobank data can be requested via the official website https://www.ukbiobank.ac.uk.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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