A study to Prevent Vascular diseases in HIV positive patients

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2017/10/010020
• Date of registration: 06-10-2017
• Prospective Registration: Yes
• Primary sponsor: NIH
• Public title: A study to Prevent Vascular diseases in HIV positive patients
• Scientific title: Randomized Trial to Prevent Vascular Events in HIV
• Date of first enrolment: 01-01-2018
• Target sample size: 6500
• Recruitment status: Open to Recruitment
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=20140
• Study type: Interventional
• Study design: Randomized, Parallel Group, Placebo Controlled Trial; Method of generating randomization sequence:Computer generated randomization Method of allocation concealment:Other Blinding and masking:Open Label
• Phase: Phase 4

Countries of recruitment

India, South Africa

Contacts

• Name: Dr N KUMARASAMY
• Affiliation: YRGCARE MEDICAL CENTRE

• Name: Dr N KUMARASAMY
• Affiliation: YRGCARE MEDICAL CENTRE

Key inclusion & exclusion criteria

Inclusion criteria: 1.Documentation ofHIV-1 infection by means of any one of the following:

.Documentation of HIV diagnosis in the medical record by a licensed health care provider;



• OR HIV-1 RNA detection by a licensed HIV-1 RNA assay demonstrating >1000 RNA copies/mL;



• OR any licensed HIV screening antibody and/or HIV antibody/antigen combination assay confirmed by a second licensed HIV assay such as a HIV-1 Western blot confirmation or HIV rapid Multispot antibody differentiation assay.



2. Combination antiretroviral therapy (ART) for at least 180 days prior to study entry.



3. CD4+ cell count >100 cells/mm3 obtainedwithin 180 days prior to study entry.



4. Laboratory values drawn at screen and/or obtained from clinical care (as indicated in section 6.1 Schedule of Events) within 90days prior to study entry.



• Fasting LDL cholesterol as follows



ASCVD RISK SCORE LDL CHOLESTEROL

<7.5% <190

>7.5%- <10% <160

>10%- >15% <130



If LDL Less that 70mg/dl participant is eligible regardless of ASCVD RISK SCORE



• Fasting triglycerides <500 mg/dL



• Hemoglobin ï?³8 g/dL for female subjects and ï?³9 g/dL for male subjects



• Calculated creatinine clearance (CrCl) ï?³60 mL/min OR Glomerular filteration rate (GFR)more than 60 ml/min/1.73m2



• ALT <=2.5 x ULN



NOTE:Subjects co-infected with chronic active hepatitis B or C must have ALT <=2 x ULN.



5. For persons with known chronic active hepatitis B or C, calculated FIB-4 score must be <=3.25.



NOTE: Active is defined as hepatitis B surface antigen positive, hepatitis B DNA positive, or hepatitis C RNA positive.

6. Female subjects of reproductive potential (defined as women who have not been post-menopausal for at least 24 consecutive months, ie, who have had menses within 24 months prior to study entry, and women who have not undergone surgical sterilization, specifically hysterectomy or bilateral oophorectomy) must have a negative serum or urine pregnancy test within 48 hours prior to entry



NOTE: Subject-reported history is considered acceptable documentation of hysterectomy, bilateral oophorectomy, andmenopause. Women are considered menopausal if they have not had a menses for at least 12 months and have a FSH (follicle stimulating hormone) of greater than 40 IU/L or, if FSH testing is not available, they have had amenorrhea for 24 consecutive months.



7. For women of reproductivepotential, willingness to use contraceptives as describedin the product information for pitavastatin. Contraceptives must be used at least two weeks before initiation of study drug and must be continued 6 weeks after cessation of study drug.



If participating in sexual activity that could lead to pregnancy, women must use a form of contraceptive. At least one of the following methods must be used appropriately:

• Condoms (male or female) with or withoutspermicidal agent

• Diaphragm or cervical cap with spermicidal agent

• Intrauterine device (IUD)

• Hormone-based contraceptive

• Tubal ligation

• Tubal micro-inserts



Women who are not of reproductive potential as defined
Exclusion criteria: 1.Clinical ASCVD, as defined by 2013 ACC/AHA guidelines, including a previous

diagnosis of any of the following:

• AMI

• Acute coronary syndromes

• Stable or unstable angina

• Coronary or other arterial revascularization

• Stroke

• TIA

• Peripheral arterial disease presumed to be of atherosclerotic origin



2.Current diabetes mellitusif LDL >=70mg/dL



NOTE: Current diabetes is defined by patient report of physician diagnosis. Subjects with a history of diabetes which has resolved and no longer requires therapy are not considered to have current diabetes, eg,women with a history of gestational diabetes, steroid-induced or medication-induced.



3. 10-year ASCVD risk score estimated by Pooled Cohort Equations >15%



4. Active cancer within 12 months prior to study entry.



5. Known decompensated cirrhosis.



6.History of myositis or myopathy with active disease in the 180 days prior to study entry.



7.Known untreated symptomatic thyroid disease.



8.History of allergy or severe adverse reaction to statins.



9.Use of specific immunosuppressants or immunomodulatory agents including but not limited to tacrolimus, sirolimus, rapamycin, mycophenolate, cyclosporine, TNF-alpha blockers or antagonists, azathioprine, interferon, growth factors, or intravenous immunoglobulin (IVIG) in the 30 days prior to study entry.



NOTE: Use of oral prednisone <=10mg/day is allowed.

10Current use of erythromycin, colchicine, or rifampin.



11 Use of statin drugs or gemfibrozil, PCSK9 inhibitors in the 90 days prior to study entry.



NOTE: Use of niacin as part of a multivitamin is not exclusionary.



12. Current use of an investigational new drugthat would be contraindicated.



13.Serious illness or trauma requiring systemic treatment or hospitalization in the 30 days prior to study entry.



14.Known active or recent (not fully resolved within 30 days prior to study entry) systemic bacterial, fungal, parasitic, or viral infections (except HIV, HBV, human papillomavirus [HPV], or HCV).



15.Current breastfeeding.



16. Alcohol or drug use that, in the opinion of the site investigator, would interfere with completion of study procedures.



17.Other medical, psychiatric, or psychological condition that, in the opinion of the site investigator, would interfere with completion of study procedures and or adherence to study drug.







Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- HIV POSITIVE

Intervention(s)

Intervention1: PITAVASTATIN: 4MG tablets administered orally
Control Intervention1: PLACEBO OF PITAVASTATIN: 4MG administered orally

Primary Outcome(s)

Statin therapy will prevent atherosclerotic cardiovascular disease (ASCVD)-related MACE (major adverse cardiovascular events) in HIV-infected persons on antiretroviral therapy (ART) in whom traditional CVD risk is not significantly increasedTimepoint: Individual subject to be followed for up to 72 months

Secondary Outcome(s)

1.Statin therapy will be associated with reductions in specific CVD-related events and all-cause mortality.



2.Decreases in LDL and non-HDL cholesterol levels associated with statin therapy will be predictive of reduction in CVD events.



3. Statin therapy will reduce serious non-cardiovascular events, including malignancies, end stage kidney or liver disease.

4. Statin therapy will be safe and welltolerated in the HIV-infected population.



Timepoint: Individual subject will be followed for up to 72 months

Secondary ID(s)

NIL

Source(s) of Monetary Support

NATIONAL INSTUTUTE OF HEALTH, MARY LAND ,USA

Ethics review

Status: Approved
Approval date: 29/05/2017
Contact:

VHS YRGCARE IRB