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Anti-Retrovirals for Kaposi's Sarcoma (ARKS)

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.
 
ClinicalTrials.gov Identifier: NCT00444379
Recruitment Status : Completed
First Posted : March 7, 2007
Last Update Posted : August 20, 2014
Sponsor:
Collaborators:
National Institutes of Health (NIH)
Gilead Sciences
Abbott
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of California, San Francisco

Tracking Information
First Submitted Date  ICMJE March 6, 2007
First Posted Date  ICMJE March 7, 2007
Last Update Posted Date August 20, 2014
Study Start Date  ICMJE April 2007
Actual Primary Completion Date February 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 24, 2012)
Blinded assessment of the change in the burden of KS lesions
survival
Original Primary Outcome Measures  ICMJE
 (submitted: March 6, 2007)
Blinded assessment of the change in the burden of KS lesions
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 16, 2007)
  • CD4+ T cell count and HIV plasma HIV RNA levels
  • KSHV DNA levels in saliva and blood
  • Humoral and cellular KSHV immune response markers
  • Quality-of-life assessment
  • Incidence of Kaposi's sarcoma-associated Immune Reconstitution Inflammatory Syndrome (KS-IRIS)
Original Secondary Outcome Measures  ICMJE
 (submitted: March 6, 2007)
  • • CD4+ T cell count and HIV plasma HIV RNA levels
  • KSHV DNA levels in saliva and blood
  • Humoral and cellular KSHV immune response markers
  • Quality-of-life assessment
  • Incidence of Kaposi's sarcoma-associated Immune Reconstitution Inflammatory Syndrome (KS-IRIS)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Anti-Retrovirals for Kaposi's Sarcoma
Official Title  ICMJE A Randomized Comparison of Protease Inhibitor-based Versus Non-nucleoside Reverse Transcriptase Inhibitor-based Antiretroviral Therapy for Initial Treatment of Individuals With AIDS-related Kaposi's Sarcoma in Sub-Saharan Africa
Brief Summary The primary purpose of this study is to determine whether a protease inhibitor-based antiretroviral regimen is more efficacious than a non-nucleoside reverse transcriptase inhibitor-based antiretroviral regimen in promoting the regression of KS tumor burden in persons with AIDS-related KS in Africa.
Detailed Description With the advent of the HIV epidemic, Kaposi's sarcoma (KS) is now the most common adult cancer in many parts of sub-Saharan Africa. In HIV-infected patients with KS in developed settings, the initiation of highly active anti-retroviral therapy (HAART) has been associated with regression of the tumor, in many but not all cases, even in the absence of conventional chemotherapy. However, it is not known which specific antiretroviral drugs or regimens are critical to convey HAART's anti-KS effect. In particular, it is not known whether the anti-KS effects of protease inhibitors (PI) in vitro and in animal models translate into improved clinical outcomes as compared to non-PI-based HAART regimens. To address this, we will determine whether a PI-based HAART regimen (lopinavir/ritonavir plus emtricitabine/tenofovir) is superior to a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART regimen (efavirenz plus emtricitabine/tenofovir) in promoting the regression of KS tumor burden in persons with AIDS-related KS in sub-Saharan Africa. We will enroll 224 patients with AIDS-related KS in Kampala, Uganda, randomly assign them to either a PI-based HAART or an NNRTI-based HAART regimen, and observe them for one year to determine the response in their KS to therapy.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Kaposi's Sarcoma
  • HIV Infections
Intervention  ICMJE Drug: Lopinavir/ritonavir plus Emtricitabine/Tenofovir versus Efavirenz plus Emtricitabine/Tenofovir
Lopinavir/ritonavir 200/50mg plus Emtricitabine/Tenofovir 200/300mg versus Efavirenz 600mg plus Emtricitabine/Tenofovir 200/300mg
Other Names:
  • Lopinavir/ritonavir Aluvia (ALUABT)
  • Efavirenz Stocrin (EFVBMM)
  • Emtricitabine/Tenofovir Truvada (TRUGLD)
Study Arms  ICMJE
  • Active Comparator: PI-based HAART regimen
    PI-based HAART regimen (lopinavir/ritonavir plus emtricitabine/tenofovir)
    Intervention: Drug: Lopinavir/ritonavir plus Emtricitabine/Tenofovir versus Efavirenz plus Emtricitabine/Tenofovir
  • Active Comparator: non-nucleoside reverse transcriptase inhibitor
    non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART regimen (efavirenz plus emtricitabine/tenofovir)
    Intervention: Drug: Lopinavir/ritonavir plus Emtricitabine/Tenofovir versus Efavirenz plus Emtricitabine/Tenofovir
Publications * Not Provided

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: March 6, 2007)
224
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 2012
Actual Primary Completion Date February 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age 18 years or older
  • HIV-1 infection
  • No prior antiretroviral therapy of any duration, including prior use to prevent perinatal transmission within prior six months.
  • No prior chemotherapy or radiotherapy for KS
  • Presence of Kaposi's sarcoma, documented by biopsy by the Pathology Department at Mulago Hospital, with at least one mucocutaneous lesion (including oral or genital mucosal lesions), each at least 0.6 x 0.6 cm in perpendicular diameters.
  • Laboratory values obtained within 21 days prior to randomization: absolute neutrophil count equal to or more than 1000/mm3; hemoglobin > 9.0 g/dL; platelet count > 50,000/mm3; creatinine < 2 times upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 times ULN; and alkaline phosphatase and total bilirubin < 2 times ULN.
  • In women, negative urine pregnancy test within 28 days of randomization and just before randomization.
  • If a woman of child-bearing potential (i.e., not yet reached menopause or undergone hysterectomy, bilateral oophorectomy, or tubal ligation), must be willing to use at least two of the following methods of contraception, to be provided by the study: condoms (male or female), IUD, or hormone-based therapy, e.g., contraceptive pills, Norplant or Depo-Provera.
  • Candidate currently resides within Uganda and does not intend to relocate away from current geographical area of residence for the duration of study participation.
  • Karnofsky performance score of 70 or more

Exclusion Criteria:

  • Extensive degree of mucocutaneous KS, which would typically require chemotherapy or radiotherapy. This is defined by any of the following:

    • One or more bulky cutaneous lesions, defined as at least 5.0 cm in greatest diameter across the surface of the skin and at least 3 cm in height
    • One or more mucocutaneous lesions exhibiting ulceration
    • One or more oral lesions that interfere with swallowing
  • Suggestion of pulmonary or gastrointestinal visceral KS, as evidenced by any of the following:

    • Abnormal chest x-ray within 21 days prior to randomization which is otherwise unexplained, unless the x-ray is unchanged compared with at least 60 days earlier
    • Positive occult blood stool testing within 21 days prior to randomization or history of overt bleeding from the mouth or rectum in the 21 days prior to randomization
  • Facial lymphedema or lymphedema in any other body region which causes symptoms (e.g., pain) or functional disability (e.g., any less than 85% active range of motion in a large joint)
  • Evidence of currently active, untreated opportunistic infection or malignancy (not including Kaposi's sarcoma); or unexplained temperature which is > 38.5 degrees C
  • Use of drugs, within the prior 28 days, contraindicated while taking lopinavir/ritonavir or efavirenz because of effects on the cytochrome P450 system. These include propafenone, astemizole, terfenadine, rifampin, rifapentine, ergot derivatives, cisapride, lovastatin, simvastatin, pimozide, midazolam, and triazolam.
  • Active drug or alcohol use that, in the investigators' opinion, would interfere with study participation
  • Breastfeeding
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 Uganda
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00444379
Other Study ID Numbers  ICMJE NIH/NCI Grant #: R01 CA119903
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of California, San Francisco
Study Sponsor  ICMJE University of California, San Francisco
Collaborators  ICMJE
  • National Institutes of Health (NIH)
  • Gilead Sciences
  • Abbott
  • Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Dr. Jeffrey N Martin, MD, MPH University of California, San Francisco
Principal Investigator: Dr. Edward K Mbidde, MBChB, MMed MRC/UVRI Uganda Research Unit on Aids
PRS Account University of California, San Francisco
Verification Date August 2014

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