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Kaletra-isentress Treatment Evaluation (KITE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00700115
Recruitment Status : Completed
First Posted : June 18, 2008
Results First Posted : October 22, 2013
Last Update Posted : December 12, 2014
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Ighovwerha Ofotokun, Emory University

Tracking Information
First Submitted Date  ICMJE June 16, 2008
First Posted Date  ICMJE June 18, 2008
Results First Submitted Date  ICMJE June 7, 2012
Results First Posted Date  ICMJE October 22, 2013
Last Update Posted Date December 12, 2014
Study Start Date  ICMJE June 2008
Actual Primary Completion Date January 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 15, 2013)
Plasma Viral Loads (HIV-1 RNA PCR) [ Time Frame: baseline to week 48 ]
Percentage subjects with undetectable Plasma viral loads
Original Primary Outcome Measures  ICMJE
 (submitted: June 17, 2008)
To assess the durability of virologic suppression (proportion of patients with plasma HIV-1 RNA PCR <50 copies/ml) with LPV/r + RAL from baseline through week 48 as compared to standard HAART regimen. [ Time Frame: 48 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 15, 2013)
To Compare Plasma Triglyceride Levels at 48 Weeks Between LPV/r + RAL and Standard HAART Treated Subjects [ Time Frame: 48 weeks ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 17, 2008)
To assess the tolerability of combination therapy with LPV/r + RAL (as defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events toxicity grading scale for symptoms and laboratory abnormalities) [ Time Frame: 48 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Kaletra-isentress Treatment Evaluation
Official Title  ICMJE A Pilot Study to Assess the Safety, Efficacy, and PK Profile of a Switch in Antiretroviral Therapy to a RTI Sparing Combination of LPV/r and RAL in Virologically Suppressed HIV-infected Patients
Brief Summary

This study will examine the effectiveness and safety of raltegravir (isentress) when used together with lopinavir/ritonavir (kaletra) for the treatment of HIV-infection. Isentress is a recently, Food and Drug Administration (FDA) approved, HIV medication that has strong effects against the HIV virus. Isentress has been shown in other studies to be safe and well tolerated by HIV patients. Combining this drug with kaletra might enable us to construct a HIV regimen that does not include the more toxic drugs of the nucleoside reverse transcriptase inhibitor class.

Eligible volunteers will undergo the following as part of the study procedure:

  1. Sign the study consent form and the HIPAA Authorization Form.
  2. Two-third of subjects, the intervention group (selected by random chance) will have their HIV drug treatment changed to kaletra + isentress.
  3. The other one-third will continue their usual HIV medications (this will be the control group).
  4. Make 9 study related visits to the Ponce clinic during the 48 weeks study period. During these visits, medical information will be collected, and blood tests will be performed.
  5. Perform Dexa-scan on two separate occasions at Emory University Hospital Radiology.

Information collected will be used to assess the effectiveness of this treatment in keeping the HIV virus suppressed, how well these two drugs together is tolerated by HIV-infected patients, and the blood levels of these two drugs when given together.

Detailed Description

RATIONALE: Virologic failure and adverse effects associated with current highly active antiretroviral therapy (HAART) warrant continuing search for novel combination therapeutic options. Raltegravir's (RAL) was recently shown to be a potent antiretroviral (ARV) agent with a favorable safety profile. If future reports continue to show positive data on this first-in-class integrase inhibitor, there may be a paradigm shift in the currently recommended first line HAART to regimens that will include integrase inhibitors.

Combining RAL with a drug that has a high genetic barrier to resistance, such as lopinavir/ritonavir (LPV/r) may offer a number of advantages. Both agents are potent and should produce durable virologic suppression. Because their combination is reverse transcriptase inhibitor (RTI) class sparing, its tolerability might be superior. In addition, RAL is not metabolized by the cytochrome P-450 enzymes, therefore, a compatible pharmacokinetic profile is expected with this combination. Pairing LPV/r with RAL in early ARV regimens as is proposed in this application may provide a HAART regimen that is highly efficacious and durable, with less resistance and adverse drug events.

DESIGN: This is single center, open label, randomized, controlled, study designed to assess the tolerability, pharmacokinetic compatibility, and the durability of virologic suppression of the RTI sparing combination therapy of LPV/r + RAL. HIV-infected subjects who are virologically suppressed (HIV-RNA PCR < 50 copies/ml) on current HAART regimen will be randomized in a 2:1 fashion to be switched to a regimen consisting of LPV/r + RAL, intervention arm A (n=40), or to be continued on their pre-study HAART regimen, control arm B (n=20). The primary endpoint will be proportion of subjects with sustained virologic suppression (HIV-1 RNA PCR < 50 copies/ml) through week 48. The immunoreconstitution, toxicity profile, and pharmacokinetic profile of the RAL and LPV/r in this novel combination therapy will be evaluated.

DURATION: 48 weeks after the enrollment of the last participant. Enrollment is expected to take about 10 months.

SAMPLE SIZE: 60 subjects.

POPULATION: HIV-infected individuals (male and female), Age > 18 years, who are virologically suppressed (HIV-RNA PCR < 50 copies/ml) on their current HAART regimen for > 6 months.

REGIMEN: For Arm A= LPV/r 400/100 mg (2 tablets) twice daily + RAL 400 mg (1 tablet) twice daily taken by mouth. For Arm B=Pre-study HAART regimen.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV Infections
Intervention  ICMJE
  • Drug: Kaletra + Isentress
    Kaletra 400/100 mg + Isentress 400 mg BID
    Other Names:
    • Raltegravir
    • Lopinavir/ritonavir
  • Drug: Pre-study antiretroviral regimen
    Standard doses of pre-study antiretroviral regimen
    Other Name: HAART
Study Arms  ICMJE
  • Experimental: Kaletra + Isentress
    Kaletra + Isentress
    Intervention: Drug: Kaletra + Isentress
  • Active Comparator: Standard HAART
    Pre-study Antiretroviral regimen
    Intervention: Drug: Pre-study antiretroviral regimen
Publications * Ofotokun I, Sheth AN, Sanford SE, Easley KA, Shenvi N, White K, Eaton ME, Del Rio C, Lennox JL. A switch in therapy to a reverse transcriptase inhibitor sparing combination of lopinavir/ritonavir and raltegravir in virologically suppressed HIV-infected patients: a pilot randomized trial to assess efficacy and safety profile: the KITE study. AIDS Res Hum Retroviruses. 2012 Oct;28(10):1196-206. Epub 2012 Apr 20.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 17, 2008)
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 2011
Actual Primary Completion Date January 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • HIV-1-infected individuals receiving HAART regimen (if on PI-based regimen, must be 1st PI-containing HAART).
  • They must have been on and tolerating current HAART regimen for > 6-months.
  • Plasma HIV-1 viral load < 50 copies/ml at study entry.
  • Men and women age > 18 years (sex is defined as sex at birth).
  • Laboratory values obtained within 30 days prior to study entry:

    • Hemoglobin > 9.4 g/dl
    • Creatinine < 2 mg/dl
    • AST (SGOT) < 2 x ULN
    • ALT (SGPT) < 2 x ULN
  • Ability and willingness of subject or legal guardian/representative to give written informed consent.
  • No CD4 T-cell counts requirement

Exclusion Criteria:

  • Subjects with a history of previous intolerance to or virological failure to LPV/r
  • Concomitant drugs (including alternative therapies) that may affect PI or RAL plasma concentrations (inducers or inhibitors of the CYP 3A4 or UDP-glucuronosyltransferase iso-enzymes).
  • A known history of noncompliance with medications or a known history of noncompliance with scheduled physician and clinic visits.
  • Investigational ARV drug.
  • Pregnancy/Breast feeding.
  • HBV-coinfected patients receiving nucleoside analogue for both HIV and HBV suppression.
  • Active drug or alcohol use or dependence which, in the Investigator's opinion, may interfere with adherence to study requirements or endanger subject's health while on the study.
  • Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to the screening visit.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 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 United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00700115
Other Study ID Numbers  ICMJE IRB00006876
KITE-6876 ( Other Identifier: Other )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ighovwerha Ofotokun, Emory University
Study Sponsor  ICMJE Emory University
Collaborators  ICMJE
  • Abbott
  • Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Igho Ofotokun, MD, MSc Emory University
PRS Account Emory University
Verification Date November 2014

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