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

NCT01683656 | Terminated Phase 4 DMC

• 1 other identifier: NILACH 2012DR4097
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

HIV; Atherosclerosis

Keywords

HIV; Atherosclerosis; Niacin/laropiprant; HDL

Outcome Measures

Primary Outcomes (1)

• change in mean common carotid intima-media thickness

  mean of maximal IMT value will be calculated over three cardiac cycles and for left and right carotid artery at baseline and week 48. The primary endpoint will be assessed by a single investigator in a blinded and anonymized fashion at cIMT Core Facility, Department of Medicine, Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada Responsible: Pr Jean-Claude Tardif.

  48 weeks

Secondary Outcomes (4)

• Mean hs-CRP plasma concentration changes

  12, 24, 48 weeks

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

  12, 24, 48 weeks

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

  12, 24, 48 weeks

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

  one year

Study Arms (2)

ER Niacin/laropipant

ACTIVE COMPARATOR

ER niacin/laropiprant 1g/20 mg for the first 4 weeks and 2g/40mg from week 5 to the end of the study.

Drug: niacin/laropiprant

ER Niacin/laropipant Placebo

PLACEBO COMPARATOR

ER niacin/laropiprant placebo p.m.

Drug: Placebo

Interventions

niacin/laropiprant DRUG

Also known as: Tredaptive

ER Niacin/laropipant

Placebo DRUG

Procedures for the manufacturing and testing of the placebo are compiled in the IMP/study drug dossier and comply with local regulatory requirements (by GMP certified manufacturer).

ER Niacin/laropipant Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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;

Sponsors & Collaborators

• Calmy Alexandra: lead
• University Hospital, Geneva: collaborator
• Swiss National Science Foundation: collaborator
• Fondation Ernest Boninchi: collaborator
• Swiss Heart Foundation: collaborator

Study Sites (7)

University Hospital Basel

Basel, Canton of Basel-City, 4031, Switzerland

Location

University Hospital Berne Inselspital

Bern, Canton of Bern, 3010, Switzerland

Location

University Hospitals Genève

Geneva, Canton of Geneva, 1211, Switzerland

Location

Kantonsspital St Gallen

Sankt Gallen, Canton of St. Gallen, 9007, Switzerland

Location

CHUV Cantonal University Hospital Vaud

Lausanne, Canton of Vaud, 1011, Switzerland

Location

University Hospital Zurich

Zurich, Canton of Zurich, Switzerland

Location

EOC Ente Ospedaliero Cantonale, civico

Lugano, Canton Ticino, 6903, Switzerland

Location

Related Publications (25)

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MeSH Terms

Conditions

Atherosclerosis

Interventions

Niacin; MK-0524

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Alexandra Calmy, MD

  University Hospital, Geneva

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of HIV Unit

Study Record Dates

• First Submitted: August 31, 2012
• First Posted: September 12, 2012
• Study Start: August 1, 2012
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: October 8, 2019

Record last verified: 2019-10

Locations

CH (7)