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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

August 31, 2012
March 14, 2013
August 2012
July 2014   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01683656 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
ER Niacin/Laropiprant Impact on Cardiovascular Markers and Atheroprogression in HIV-infected Individuals on cART
ER Niacin/Laropiprant Impact on Cardiovascular Markers and Atheroprogression in HIV-infected Individuals on cART

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.

Not Provided
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • HIV
  • Atherosclerosis
  • Drug: niacin/laropiprant
    Other Name: Tredaptive
  • 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).
  • 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.
    Intervention: Drug: niacin/laropiprant
  • Placebo Comparator: ER Niacin/laropipant Placebo
    ER niacin/laropiprant placebo p.m.
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
4
July 2014
July 2014   (final data collection date for primary outcome measure)

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.
Both
40 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Switzerland
 
NCT01683656
NILACH 2012DR4097
Yes
Calmy Alexandra, University Hospital, Geneva
Calmy Alexandra
  • University Hospital, Geneva
  • Swiss National Science Foundation
  • Fondation Ernest Boninchi
  • Swiss Heart Foundation
Principal Investigator: Alexandra Calmy, MD University Hospitals Geneva
University Hospital, Geneva
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP