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ER Niacin/Laropiprant Impact on Cardiovascular Markers and Atheroprogression in HIV-infected Individuals on cART

Information source: University Hospital, Geneva
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: HIV; Atherosclerosis

Intervention: niacin/laropiprant (Drug); Placebo (Drug)

Phase: Phase 4

Status: Terminated

Sponsored by: Calmy Alexandra

Official(s) and/or principal investigator(s):
Alexandra Calmy, MD, Principal Investigator, Affiliation: University Hospitals Geneva

Summary

HIV-infected patients are at increased risk for cardiovascular disease. Large investigations support an inverse correlation between HDL-C levels and coronary heart disease. Therefore a treatment lowering HDL-C such as niacin could reduce the risk of atheroprogression not only through its benefit in terms of lipid profile, but also by reducing atherosclerotic inflammation. The study aims at showing that a therapy targeting HDL-C increase in HIV-infected patients on suppressive cART has the potential for reducing subclinical atherosclerotic inflammation associated with HIV itself in HIV-individuals on cART. NILACH is a randomised, multicenter, double blind, placebo controlled, 48 weeks trial to test the effect of the newly marketed niacin/laropiprant on carotid intima-media thickness (IMT) in 90 subjects.

- Regimen 1: ER niacin/laropiprant 1g/20 mg for the first 4 weeks and 2g/40mg from week 5

to the end of the study (the titration aims to reduce adverse reactions)

- Regimen 2: ER niacin/laropiprant placebo p. m.

The primary end point is the change in mean common carotid intima-media thickness from baseline and 48 weeks, compared between the niacin/laropiprant group and the placebo group. The proposed in vivo experiments should provide insights on the potential benefits of niacin treatment of cardiovascular disease in HIV patients. In addition, we will be able to further clarify the role of systemic inflammatory mediators in the development of early atherosclerosis of HIV-infected patients on antiretroviral therapy. Detection and treatment of non-infectious co-morbidities such as cardiovascular diseases have become essential for HIV-infected individuals exposed to lifelong antiretroviral therapy and go beyond mere management of opportunistic infections or virologic suppression.

Clinical Details

Official title: ER Niacin/Laropiprant Impact on Cardiovascular Markers and Atheroprogression in HIV-infected Individuals on cART

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: change in mean common carotid intima-media thickness

Secondary outcome:

Mean hs-CRP plasma concentration changes

Mean Total Cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, apolipoprotein, triglycerides, and apolipoprotein (apo) Al, B and E levels

Mean biomarkers of inflammatory process (fibrinogen, S-VCAM-1, adiponectin, CCL2, CCL3, d-dimer, IL-6, TNF-alpha, Lp-PLA2) changes

Clinical MACE: cardiovascular mortality, stroke, acute coronary syndromes, any cardiac arrhythmias, hospitalisation for cardiovascular causes, peripheral artery disease, revascularization.

Eligibility

Minimum age: 40 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Adult patients > 40 years;

- Women of childbearing potential must use two reliable contraceptive methods during

the entire trial, from day 1 to one month after the end of the trial.

- Signing the study consent form;

- Stable cART since at least 3 months (ie no recent drug change);

- HIV-RNA below 100 copies for at least 6 months;

- HDL-cholesterol <1. 29 mmol/l for men; <1. 42 mmol/l for women

Exclusion Criteria:

- Pregnancy or lactation;

- Congestive Heart Failure;

- Malignant Hypertension;

- Acute or chronic coronary artery diseases;

- Any known cardiac arrhythmias;

- Diabetes;

- Concomitant cancer, rheumatologic disease or inflammatory bowel diseases;

- Concomitant renal or hepatic disease:

- Creatinine above 150 micromol/L

- Transaminases above 5 times upper normal limit

- Prothrombin time (Quick) value below 50%;

- Prior intolerance to niacin therapy (reported in a medical report);

- Cyclosporine, anti-inflammatory drugs (other than aspirin) or cytokine therapy in

concomitant intake;

- Abnormal thyroid function;

- Excessive consumption of alcohol;

- Known severe lactose intolerance.

Locations and Contacts

University Hospital Berne Inselspital, Berne, BE 3010, Switzerland

University Hospital Basel, Basel, BS 4031, Switzerland

University Hospitals Genève, Geneva, GE 1211, Switzerland

Kantonsspital St Gallen, St Gallen, SG 9007, Switzerland

EOC Ente Ospedaliero Cantonale, civico, Lugano, TI 6903, Switzerland

CHUV Cantonal University Hospital Vaud, Lausanne, VD 1011, Switzerland

University Hospital Zurich, Zurich, ZH, Switzerland

Additional Information

Related publications:

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Starting date: August 2012
Last updated: March 14, 2013

Page last updated: August 23, 2015

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