Coronary Artery DiseasePhase 4PROACT 2NCT05850091
Polygenic Risk-based Detection of Subclinical Coronary Atherosclerosis and Intervention With Statin and Colchicine
A Phase 4 study testing Rosuvastatin and Colchicine in people with Coronary Artery Disease, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
The goal of this double-blind randomized controlled trial is to determine how treatment with high intensity statin, low-dose colchicine, and their combination modulates progression and composition of coronary atherosclerosis in individuals with high polygenic risk for coronary artery disease. Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Coronary Artery Disease
- What is being tested?
- Rosuvastatin and Colchicine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Dec 2023to 1 Jun 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females between 40 and 75 years of age capable and willing to provide informed consent
- Participant has high CAD PRS as defined on a clinical test
- Participant with subclinical atherosclerosis defined as plaque visible on CCTA and causing <70% luminal stenosis
Who cannot join
- Participant with a history of cardiovascular disease, defined by a diagnosis of coronary artery disease, peripheral artery disease, or cerebrovascular disease
- Participant with a history of Liver disease (cirrhosis, active hepatitis, or severe hepatic disease) or any of the following recent lab results and determined to be non-transient: alanine aminotransferase greater than 3 times the upper limit of normal or total bilirubin greater than 2 times the upper limit of normal (unless due to Gilbert syndrome)
- Participant with estimated glomerular filtration rate <60 mL/min/1.73 m2 or creatinine greater than 2 times the upper limit of normal
- Patient with history of an allergic reaction or significant sensitivity to iodinated contrast, colchicine, or statins
- Patient currently taking LDL cholesterol lowering or anti- inflammatory medications including colchicine
- Participants requiring regular drugs known to be potent CY2P inhibitors (eg. ketoconazole, clarithromycin)
Show all 10Show fewer
- Female patient who is pregnant, or breast-feeding or is considering becoming pregnant during the study
- Participant with BMI ≥ 40 kg/m2
- Participant unable to provide informed consent
- Participant unable to hold breath for 10 seconds
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
The goal of this double-blind randomized controlled trial is to determine how treatment with high intensity statin, low-dose colchicine, and their combination modulates progression and composition of coronary atherosclerosis in individuals with high polygenic risk for coronary artery disease.
Read the detailed description
The main question PROACT 2 aims to answer is whether and how single or dual targeting of cholesterol-lowering and inflammation modulates coronary plaque in individuals with high polygenic risk and subclinical coronary atherosclerosis.
This is a double-blind randomized controlled trial of 200 individuals with high polygenic risk for coronary artery disease and subclinical plaque on coronary computed tomography angiography. Participants will be randomized into four equal treatment groups: group A receiving a placebo daily, group B receiving rosuvastatin 20mg daily, group C receiving colchicine 0.6mg daily, and group D receiving both rosuvastatin 20mg daily and colchicine 0.6mg daily. The primary outcome is change in total non-calcified plaque volume on coronary computed tomography angiography from baseline to one year. Multiple secondary plaque imaging and biomarker outcomes will be explored in this pilot mechanistic trial.
- Conditions
- Coronary Artery Disease
- Being tested
- Rosuvastatin, Colchicine, Placebo
- Keywords
- Polygenic risk, Atherosclerosis, Genetics, Genomic medicine, Polygenic score, Precision medicine, Preventive cardiology, Coronary plaque, Inflammation, Cholesterol, Lipids, Colchicine, Statin
- Medical subject headings
- Coronary Artery Disease, Atherosclerosis, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RosuvastatinDrug
Pharmacotherapy for reduction in LDL cholesterol level
ColchicineDrug
Pharmacotherapy for inflammation inhibition
PlaceboDrug
Capsule with sugar pill that mimics active study drugs
| Study group | Role | What they receive |
|---|---|---|
| Group A | Placebo comparator | Participants will receive placebo daily Receives: Drug: Placebo |
| Group B | Active comparator | Participants will receive rosuvastatin 20mg daily and placebo daily Receives: Drug: Rosuvastatin; Drug: Placebo |
| Group C | Active comparator | Participants will receive colchicine 0.6mg daily and placebo daily Receives: Drug: Colchicine; Drug: Placebo |
| Group D | Active comparator | Participants will receive rosuvastatin 20mg daily and colchicine 0.6mg daily Receives: Drug: Rosuvastatin; Drug: Colchicine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in total non-calcified plaque volume from baseline to one year
The primary outcome of this study is the change in total non-calcified plaque volume between the two groups from baseline to one year. This outcome will be measured using coronary computed tomography angiography (CCTA) and reported in cubic millimeters (mm³). The comparison of the changes in non-calcified plaque volume will help assess the effectiveness of the intervention on plaque progression and composition.
Measured: 1 year
Secondary outcomes (9)
Change in total plaque volumes from baseline to one year
The change in the following plaque volumes will be compared between the two groups from baseline to one year: total plaque volume, total calcified plaque volume, and total low attenuation plaque volume. These volumes will be analyzed individually and reported in cubic millimeters (mm³).
Measured: 1 year
Change in maximal luminal stenosis from baseline to one year
The change in maximal luminal stenosis will be compared between the two groups from baseline to one year, reported as a percentage (%).
Measured: 1 year
Change in calcium score from baseline to one year
The change in calcium score will be compared between the two groups from baseline to one year, reported in Agatston units.
Measured: 1 year
Change in number of high-risk features from baseline to one year
The change in the number of high-risk features will be compared between the two groups from baseline to one year, reported as a count (number of features).
Measured: 1 year
Change in fat attenuation index from baseline to one year
The change in fat attenuation index will be compared between the two groups from baseline to one year, reported in Hounsfield units (HU).
Measured: 1 year
Progression in non-calcified plaque volume from baseline to one year
The proportion of participants who had progression in non-calcified plaque volume from baseline to one year (%)
Measured: 1 year
Change in low-density lipoprotein cholesterol (LDL-C) from baseline to one year
The change in low-density lipoprotein cholesterol (LDL-C) will be compared between the two groups from baseline to one year, reported in milligrams per deciliter (mg/dL).
Measured: 1 year
Change in C-reactive protein (CRP) from baseline to one year
The change in C-reactive protein (CRP) will be compared between the two groups from baseline to one year, reported in milligrams per liter (mg/L).
Measured: 1 year
Change in Interleukin-6 and Interleukin-1 beta (IL-1ß) from baseline to one year
The change in Interleukin-6 (IL-6) and Interleukin-1 beta (IL-1ß) will be compared between the two groups from baseline to one year. Both biomarkers will be analyzed individually and reported in picograms per milliliter (pg/mL).
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2023
- Study start7 Dec 2023
- Primary completion1 Jun 2027 (estimated)
- Study completion1 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Akl C. Fahed, MD, MPH, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05850091
- Sponsor's protocol ID
- 2023P000945
- Acronym
- PROACT 2
- Status last verified
- Jun 2026
- First submitted
- 6 Apr 2023
- Last updated
- 12 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be tabulated and analyzed. Study site will not share any of the subject identifiers.
Publications
Abou-Karam R, Kim MS, Jemma Cho SM, Bitar F, Gady S, Cheng F, Thompson AG, Karlson EW, Natarajan P, Ellinor PT, Foldyna B, Ghebremichael MS, Atlas SJ, Ridker PM, Lu MT, Fahed AC. Polygenic Risk Based Detection and Treatment of Subclinical Coronary Atherosclerosis in the PROACT Clinical Trials. J Am Coll Cardiol. 2026 Feb 6:S0735-1097(25)10563-9. doi: 10.1016/j.jacc.2025.12.032. Online ahead of print.
PubMed 41706060
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Polygenic Risk-based Detection of Subclinical Coronary Atherosclerosis and Intervention With Statin and Colchicine
- ClinicalTrials.gov ID
- NCT05850091
- Acronym / sponsor ID
- PROACT 2 / 2023P000945
- Conditions
- Coronary Artery Disease
- Keywords
- Polygenic risk, Atherosclerosis, Genetics, Genomic medicine, Polygenic score, Precision medicine, Preventive cardiology, Coronary plaque
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 7 Dec 2023 (actual)
- Primary completion
- 1 Jun 2027 (estimated)
- Study completion
- 1 Jun 2027 (estimated)
- First posted
- 9 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this double-blind randomized controlled trial is to determine how treatment with high intensity statin, low-dose colchicine, and their combination modulates progression and composition of coronary atherosclerosis in individuals with high polygenic risk for coronary artery disease.
Detailed description
The main question PROACT 2 aims to answer is whether and how single or dual targeting of cholesterol-lowering and inflammation modulates coronary plaque in individuals with high polygenic risk and subclinical coronary atherosclerosis.
This is a double-blind randomized controlled trial of 200 individuals with high polygenic risk for coronary artery disease and subclinical plaque on coronary computed tomography angiography. Participants will be randomized into four equal treatment groups: group A receiving a placebo daily, group B receiving rosuvastatin 20mg daily, group C receiving colchicine 0.6mg daily, and group D receiving both rosuvastatin 20mg daily and colchicine 0.6mg daily. The primary outcome is change in total non-calcified plaque volume on coronary computed tomography angiography from baseline to one year. Multiple secondary plaque imaging and biomarker outcomes will be explored in this pilot mechanistic trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group A | Placebo comparator | Drug: PlaceboParticipants will receive placebo daily |
| Group B | Active comparator | Drug: Rosuvastatin, Drug: PlaceboParticipants will receive rosuvastatin 20mg daily and placebo daily |
| Group C | Active comparator | Drug: Colchicine, Drug: PlaceboParticipants will receive colchicine 0.6mg daily and placebo daily |
| Group D | Active comparator | Drug: Rosuvastatin, Drug: ColchicineParticipants will receive rosuvastatin 20mg daily and colchicine 0.6mg daily |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Males and females between 40 and 75 years of age capable and willing to provide informed consent
- Participant has high CAD PRS as defined on a clinical test
- Participant with subclinical atherosclerosis defined as plaque visible on CCTA and causing <70% luminal stenosis
Key exclusion criteria (10 listed)
- Participant with a history of cardiovascular disease, defined by a diagnosis of coronary artery disease, peripheral artery disease, or cerebrovascular disease
- Participant with a history of Liver disease (cirrhosis, active hepatitis, or severe hepatic disease) or any of the following recent lab results and determined to be non-transient: alanine aminotransferase greater than 3 times the upper limit of normal or total bilirubin greater than 2 times the upper limit of normal (unless due to Gilbert syndrome)
- Participant with estimated glomerular filtration rate <60 mL/min/1.73 m2 or creatinine greater than 2 times the upper limit of normal
- Patient with history of an allergic reaction or significant sensitivity to iodinated contrast, colchicine, or statins
- Patient currently taking LDL cholesterol lowering or anti- inflammatory medications including colchicine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RosuvastatinPharmacotherapy for reduction in LDL cholesterol level | Drug | Group B, Group D |
| ColchicinePharmacotherapy for inflammation inhibition | Drug | Group C, Group D |
| PlaceboCapsule with sugar pill that mimics active study drugs | Drug | Group A, Group B, Group C |
Primary outcome
Change in total non-calcified plaque volume from baseline to one year
Time frame: 1 year
The primary outcome of this study is the change in total non-calcified plaque volume between the two groups from baseline to one year. This outcome will be measured using coronary computed tomography angiography (CCTA) and reported in cubic millimeters (mm³). The comparison of the changes in non-calcified plaque volume will help assess the effectiveness of the intervention on plaque progression and composition.
9 secondary outcomes
Change in total plaque volumes from baseline to one year
Time frame: 1 year
Change in maximal luminal stenosis from baseline to one year
Time frame: 1 year
Change in calcium score from baseline to one year
Time frame: 1 year
Change in number of high-risk features from baseline to one year
Time frame: 1 year
Change in fat attenuation index from baseline to one year
Time frame: 1 year
Progression in non-calcified plaque volume from baseline to one year
Time frame: 1 year
Change in low-density lipoprotein cholesterol (LDL-C) from baseline to one year
Time frame: 1 year
Change in C-reactive protein (CRP) from baseline to one year
Time frame: 1 year
Change in Interleukin-6 and Interleukin-1 beta (IL-1ß) from baseline to one year
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2026.
- Derived from this study: PubMed 41706060Abou-Karam R, Kim MS, Jemma Cho SM, Bitar F, Gady S, Cheng F, Thompson AG, Karlson EW, Natarajan P, Ellinor PT, Foldyna B, Ghebremichael MS, Atlas SJ, Ridker PM, Lu MT, Fahed AC. Polygenic Risk Based Detection and Treatment of Subclinical Coronary Atherosclerosis in the PROACT Clinical Trials. J Am Coll Cardiol. 2026 Feb 6:S0735-1097(25)10563-9. doi: 10.1016/j.jacc.2025.12.032. Online ahead of print.
- Individual participant dataSharing planned: Yes. Data will be tabulated and analyzed. Study site will not share any of the subject identifiers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Rosuvastatin and Colchicine in people with Coronary Artery Disease, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 12 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in total non-calcified plaque volume from baseline to one year (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05850091, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2026.