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

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ClinicalTrials.gov Identifier: NCT01683656
Recruitment Status : Terminated (Withdrawal of IMP from the market. Data on risk-benefit ratio pending.)
First Posted : September 12, 2012
Last Update Posted : March 15, 2013
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

Tracking Information
First Submitted Date  ICMJE August 31, 2012
First Posted Date  ICMJE September 12, 2012
Last Update Posted Date March 15, 2013
Study Start Date  ICMJE August 2012
Estimated Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 7, 2012)
change in mean common carotid intima-media thickness [ Time Frame: 48 weeks ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01683656 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 7, 2012)
  • Mean hs-CRP plasma concentration changes [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 12, 24, 48 weeks ]
  • Clinical MACE: cardiovascular mortality, stroke, acute coronary syndromes, any cardiac arrhythmias, hospitalisation for cardiovascular causes, peripheral artery disease, revascularization. [ Time Frame: one year ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE ER Niacin/Laropiprant Impact on Cardiovascular Markers and Atheroprogression in HIV-infected Individuals on cART
Official Title  ICMJE ER Niacin/Laropiprant Impact on Cardiovascular Markers and Atheroprogression in HIV-infected Individuals on cART
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • HIV
  • Atherosclerosis
Intervention  ICMJE
  • 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).
Study Arms  ICMJE
  • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 14, 2013)
4
Original Estimated Enrollment  ICMJE
 (submitted: September 7, 2012)
90
Estimated Study Completion Date  ICMJE July 2014
Estimated Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01683656
Other Study ID Numbers  ICMJE NILACH 2012DR4097
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Calmy Alexandra, University Hospital, Geneva
Study Sponsor  ICMJE Calmy Alexandra
Collaborators  ICMJE
  • University Hospital, Geneva
  • Swiss National Science Foundation
  • Fondation Ernest Boninchi
  • Swiss Heart Foundation
Investigators  ICMJE
Principal Investigator: Alexandra Calmy, MD University Hospital, Geneva
PRS Account University Hospital, Geneva
Verification Date March 2013

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