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

This study has been terminated.
(Withdrawal of IMP from the market. Data on risk-benefit ratio pending.)
Sponsor:
Collaborators:
University Hospital, Geneva
Swiss National Science Foundation
Fondation Ernest Boninchi
Swiss Heart Foundation
Information provided by (Responsible Party):
Calmy Alexandra, University Hospital, Geneva
ClinicalTrials.gov Identifier:
NCT01683656
First received: August 31, 2012
Last updated: March 14, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
HIV
Atherosclerosis
Drug: niacin/laropiprant
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: ER Niacin/Laropiprant Impact on Cardiovascular Markers and Atheroprogression in HIV-infected Individuals on cART

Resource links provided by NLM:


Further study details as provided by University Hospital, Geneva:

Primary Outcome Measures:
  • change in mean common carotid intima-media thickness [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Mean hs-CRP plasma concentration changes [ Time Frame: 12, 24, 48 weeks ] [ Designated as safety issue: No ]
  • Mean Total Cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, apolipoprotein, triglycerides, and apolipoprotein (apo) Al, B and E levels [ Time Frame: 12, 24, 48 weeks ] [ Designated as safety issue: No ]
  • Mean biomarkers of inflammatory process (fibrinogen, S-VCAM-1, adiponectin, CCL2, CCL3, d-dimer, IL-6, TNF-alpha, Lp-PLA2) changes [ Time Frame: 12, 24, 48 weeks ] [ Designated as safety issue: No ]
  • Clinical MACE: cardiovascular mortality, stroke, acute coronary syndromes, any cardiac arrhythmias, hospitalisation for cardiovascular causes, peripheral artery disease, revascularization. [ Time Frame: one year ] [ Designated as safety issue: No ]

Enrollment: 4
Study Start Date: August 2012
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: ER Niacin/laropipant
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
Other Name: Tredaptive
Placebo Comparator: ER Niacin/laropipant Placebo
ER niacin/laropiprant placebo p.m.
Drug: Placebo
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).

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01683656

Locations
Switzerland
University Hospital Berne Inselspital
Berne, BE, Switzerland, 3010
University Hospital Basel
Basel, BS, Switzerland, 4031
University Hospitals Genève
Geneva, GE, Switzerland, 1211
Kantonsspital St Gallen
St Gallen, SG, Switzerland, 9007
EOC Ente Ospedaliero Cantonale, civico
Lugano, TI, Switzerland, 6903
CHUV Cantonal University Hospital Vaud
Lausanne, VD, Switzerland, 1011
University Hospital Zurich
Zurich, ZH, Switzerland
Sponsors and Collaborators
Calmy Alexandra
University Hospital, Geneva
Swiss National Science Foundation
Fondation Ernest Boninchi
Swiss Heart Foundation
Investigators
Principal Investigator: Alexandra Calmy, MD University Hospitals Geneva
  More Information

Publications:

Responsible Party: Calmy Alexandra, Head of HIV Unit, University Hospital, Geneva
ClinicalTrials.gov Identifier: NCT01683656     History of Changes
Other Study ID Numbers: NILACH 2012DR4097
Study First Received: August 31, 2012
Last Updated: March 14, 2013
Health Authority: Switzerland: Swissmedic

Keywords provided by University Hospital, Geneva:
HIV
Atherosclerosis
Niacin/laropiprant
HDL

Additional relevant MeSH terms:
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Niacin
Nicotinic Acids
Niacinamide
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Vasodilator Agents
Cardiovascular Agents
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 14, 2014