COLCHICINE for HIV infection|Coronary artery inflammation

Inclusion criteria

• {"criterion_text":"- PWH > 50 years old\n- High cardiovascular risk measured by SCORE-2 > 5%\n- Stable antiretroviral therapy (ART) in the previous six months\n- Viral load < 50 copies/mililiter for at least 1 year. One blip is allowed (Viral load between 20-200 copies/mililiter with a previous and after viral load determinations < 20 copies per mililiter.\n- CD4 cell count > 350 cells/mm3\n- Stable dose of an intermediate or high intensity statin in the previous year (statin dose should not be modified throghout the study unless there is a robust clinical indication). In case the participant does not receive statins, all other hypolipemiants (bempedoic acid, ezetimibe) will need to be at a stable dose as well in the previous year.\n- No clinical indication for a change in treatment based on European Society of Cardiology Guidelines\n- Written informed consent obtained according to international guidelines and local laws\n- Ability to understand the nature of the trial and the trial related procedures and to comply with them"}

Exclusion criteria

• {"criterion_text":"- Severe Heart failure defined as LVEF < 35%.\n- Renal dysfunctions defined as eGFR < 50 ml/min or serum creatinine levels > 1.7 mg/dL\n- Severe hepatic impairments defined as a Child-Pugh category C\n- Levels of ALT over five times the upper limit of normal OR levels of ALT over three times the upper limit of normal AND bilirrubin levels over one point five times the upper limit of normal\n- Participant is receiving drugs that inhibit the CYP3A4 (e.g. Verapamil, Azithromycin, Clarithromycin, protease inhibitors, cobicistat), CYP2D6 or inhibitors of P-glycoprotein.\n- Participant needs treatment with colchicine for any indication\n- Participants with stomach ulcers or gastrointestinal bleeding\n- Participants with highly elevated hsCRP > 10 mg/dL at screening\n- Women of childbearing potential. - Permanent sterilisation methods including hysterectomy, bilateral salpingectomy and bilateral oophorectomy. -\tPostmenopausal state, defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. -\tMale participants are considered fertile after puberty unless permanently sterile by bilateral orchiectomy. To prevent pregnancies in female partners of male participants, they must agree to use highly effective contraceptive methods or have practiced sexual abstinence during the treatment period and until the end of relevant systemic exposure, defined as 5 half-lives of the IMP (9 days approximately).\n- Known hypersensitivity to the active substances or any of the excipients\n- Known iodine contrast allergy with prior history of anaphylaxis\n- Patient without legal capacity who is unable to understand the nature, significance and consequences of the trial\n- Previous MI, stroke or coronary by-pass surgery\n- History of non-cutaneus malignancy prior to enrollment\n- History of inflammatory bowel disease or chronic diarrhoea"}

Primary endpoints

• {"endpoint_text":"- Percent change from baseline of the mean Fat Attenuation Index (FAI) score for the 3 coronary arteries (RCA, LAD, LCX), calculated as the average of the analyzable FAI scores (valid baseline and post-baseline FAI score) across the three main coronary arteries","definition_or_measurement_approach":"Percent change from baseline of mean FAI across the three coronary arteries (RCA, LAD, LCX), calculated as the average of the analyzable FAI scores (valid baseline and post-baseline FAI score) across the three arteries."}

Secondary endpoints

• {"endpoint_text":"- Changes in plaque volume and plaque burden assessed by CCTA in week 96.","definition_or_measurement_approach":"Assessed by coronary computed tomography angiography (CCTA) at week 96 to measure plaque volume and plaque burden."}
• {"endpoint_text":"- Changes in plaque morphology (non-calcified, mixed, calcified) assessed by CCTA in week 96","definition_or_measurement_approach":"Assessment of plaque morphology categories (non-calcified, mixed, calcified) by CCTA at week 96."}
• {"endpoint_text":"- Changes in the percentage of high-risk plaques (positive remodelling, spotty calcium, napky ring sign and low attenuation plaque) assessed by CCTA in week 96","definition_or_measurement_approach":"Percentage of high-risk plaques (features: positive remodelling, spotty calcium, napky ring sign, low attenuation plaque) evaluated by CCTA at week 96."}
• {"endpoint_text":"- Changes in serum inflammatory markers (hsPCR, IL-6, IL-1 beta, IL-18, SuPAR) in week 96","definition_or_measurement_approach":"Measurement of specified serum inflammatory markers (hsCRP, IL-6, IL-1β, IL-18, SuPAR) at week 96."}
• {"endpoint_text":"- Changes in inflammasome markers in extracellular vesicles (NLRP3, ASC, Caspase-1) in week 96","definition_or_measurement_approach":"Measurement of inflammasome markers (NLRP3, ASC, Caspase-1) in extracellular vesicles at week 96."}
• {"endpoint_text":"- Changes in differential monocytes subpopulations (classic CD14++CD16-, non-classic CD14++CD16++ and intermediate CD14+CD16+) in week 96","definition_or_measurement_approach":"Flow cytometry or equivalent measurement of monocyte subpopulations (classic, non-classic, intermediate) at week 96."}
• {"endpoint_text":"- Percentage change of leukocyte count in week 96","definition_or_measurement_approach":"Percentage change from baseline in total leukocyte count measured at week 96."}
• {"endpoint_text":"- Solicited and unsolicited AEs in all participants throughout the trial","definition_or_measurement_approach":"Collection and reporting of solicited and unsolicited adverse events for all participants throughout the trial duration."}
• {"endpoint_text":"- Serious adverse events (SAEs) in all participants","definition_or_measurement_approach":"Recording and assessment of serious adverse events in all participants throughout the trial."}
• {"endpoint_text":"- Change from baseline for FAI, FAI score (mean absolute change and mean percent change) and FAI score centile in the following vessels: Greatest change in most inflamed vessel, Greatest change in any vessel , RCA only analysis, LAD only analysis, LCX only analysis","definition_or_measurement_approach":"Calculation of mean absolute and percent change from baseline and centiles for FAI across specified vessel analyses (most inflamed vessel, any vessel, RCA, LAD, LCX)."}
• {"endpoint_text":"- Mean absolute change from baseline for mean FAI and mean FAI score, defined as the average of the analyzable vessels (with valid baseline FAI and post-baseline FAI) across the three main coronary arteries (RCA, LAD, LCX)","definition_or_measurement_approach":"Mean absolute change from baseline for mean FAI calculated as average of analyzable vessels (valid baseline and post-baseline) across RCA, LAD, LCX."}
• {"endpoint_text":"- Differences in FAI percentage change between males and females in both treatment groups assessed by CCTA in week 96","definition_or_measurement_approach":"Between-sex comparisons of percent change in FAI by treatment group assessed by CCTA at week 96."}
• {"endpoint_text":"- Differences in FAI percentage change by CYP2D6 genotype in the treatment group","definition_or_measurement_approach":"Comparison of percent change in FAI within treatment group stratified by CYP2D6 metabolizer genotype classification."}
• {"endpoint_text":"- Differences in MACE between colchicine and placebo groups assessed clinically in week 96","definition_or_measurement_approach":"Assessment and comparison of major adverse cardiovascular events (MACE) clinically between treatment groups at week 96."}
• {"endpoint_text":"- Change from baseline for CaRi-Heart risk score (mean absolute change and mean percent change.","definition_or_measurement_approach":"Calculation of mean absolute and percent change from baseline for CaRi-Heart risk score."}

Spain

Earliest CTIS Part Ii Submission Date

28-03-2025

Latest Decision Or Authorization Date

31-03-2026

Processing Time Days

368

Number Of Sites

4

Number Of Participants

104

Primary sponsor

Full Name

Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz

Organisation Type

Patient organisation/association

Country Of Registered Address

Spain