Evaluation of 3TC or FTC Mono-therapy Compared to Continuing HAART as a Bridging Strategy

NCT01338025 | Terminated Phase 4 Results DMC

• 2 other identifiers: IMPAACT P1094U01AI068632
• Study Type: interventional
• Target: 33
• Locations: 5 countries
• Sites: 17

Brief Summary

The purpose of this study was to compare the use of lamivudine (3TC) or emtricitabine (FTC) alone vs. continuing a failing highly active antiretroviral therapy (HAART) regimen in HIV infected children, adolescents and young adults. The study was to see if there were changes in the HIV virus and if there were differences in immune function, viral load and medication side effects between the two groups over 28 weeks. Participants were assigned to either take 3TC or FTC alone or continue on his/her current failing HAART regimen. During the first 28 weeks of this study, if the participant was randomized to the continue HAART arm, he/she was not switched to a different or new, potentially suppressive HAART regimen, but continued on the current failing HAART regimen. However, if continuing HAART, the participant might be switched to a new regimen if their provider felt that it was clinically needed or the participant met certain study endpoints (e.g., drop in CD4, increase in viral load). At the end of 28 weeks, the participant had the choice of remaining on the assigned study group medication(s) or starting a new HAART regimen prescribed by his/her doctor. Then, they would be followed for another 24 weeks to compare the difference in immune function, viral load and medication side effects between the different groups.

Conditions

HIV Disease

Keywords

HIV; Bridging; Strategy

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Immunologic Deterioration

  Immunologic deterioration was declared for a participant if any one of the following conditions is observed within the first 28 weeks: * greater than or equal to 30% decline in absolute CD4+ T cell count from entry, or * development of CDC class C events. Results report number of participants with immunologic deterioration at week 28 calculated.

  From entry to week 28

Secondary Outcomes (3)

• Change in CD4+ T Cell Count

  Entry to week 28

• Change in HIV-1 RNA Levels

  28 Weeks

• Number of Participants Non-adherent as Measured by 3-day Recall

  28 Weeks

Study Arms (2)

Arm A, non-suppressive HAART regimen

ACTIVE COMPARATOR

In Step 1, subjects were randomized to continue their non-suppressive HAART regimen. In Step 2, subjects either began a new HAART regimen, continued randomized treatment, or discontinued therapy while remaining on follow-up, as decided by their provider.

Drug: HAART regimen

Arm B, 3TC or FTC monotherapy

ACTIVE COMPARATOR

In step 1, subjects were randomized to receive 3TC or FTC (the choice of 3TC or FTC was left to the provider). In Step 2, subjects either began a new HAART regimen, continued randomized treatment, or discontinued therapy while remaining on follow-up, as decided by their provider.

Drug: 3TC or FTC monotherapy

Interventions

HAART regimen DRUG

The study participant continued their non-suppressive HAART regimen as prescribed by their primary provider.

Also known as: Highly active antiretrovial therapy (HAART)

Arm A, non-suppressive HAART regimen

3TC or FTC monotherapy DRUG

The study participant was assigned to either 3TC or FTC monotherapy (the choice of 3TC or FTC was left to the provider.

Also known as: Lamivudine (3TC), emtricitabine (FTC)

Arm B, 3TC or FTC monotherapy

Eligibility Criteria

• Age: 8 Years - 24 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age greater than or equal to 8 to less than 25 years of age, at study entry
• Documentation of HIV-1 infection defined as positive results from two samples collected at different time points
• Treatment experienced patients must have demonstrated failure on the current HAART regimen for 2 months or longer. These patients must have been on ARVs for at least a total of 6 months prior to entry. Thus, if the failing regimen was the first ARV regimen, then the patient must have been on that initial regimen for a minimum of 6 months total.
• CD4+ T cell count greater than or equal to 100 cells/mm3 (confirmed on at least two occasions within 6 months of study entry, including the screening value)
• Documentation of the M184V mutation on genotypic testing at any time prior to study entry
• In the best judgment of the clinical site team, concerns about the subject's ability to adhere made it unsuitable to initiate a new optimal HAART regimen for at least 6 months.
• Subject had not become adherent despite site's adherence interventions
• Female subjects of reproductive potential engaging in sexual activity that could lead to pregnancy had to agree to avoid pregnancy during the entire 52 week trial and to consistently and appropriately use at least two of the following contraception methods: condoms, diaphragm or cervical cap with spermicide, IUD, hormonal-based contraception. A list of acceptable methods can be found at the FDA Birth Control Guide (http://www.fda.gov/womens).
• Parent/legal guardian or subject able and willing to provide signed informed consent when applicable

You may not qualify if:

• Positive hepatitis B surface antigen or known active hepatitis B infection.
• Pregnant or breastfeeding.
• Active malignancy within the past 2 years.
• Current immunosuppressive therapy, including the equivalent of greater than 1 mg/kg/per day or greater than 20 mg total daily dose of prednisone in the 2 weeks preceding screening. Subjects for whom long-term systemic corticosteroid therapy (greater than 2 weeks) was anticipated were excluded. \[Note: non-steroidal anti-inflammatory agents and inhaled, nasal, and topical corticosteroids were not excluded as immunosuppressive therapy.\]
• Prior immunization with an HIV-specific vaccine
• Greater than or equal to 1 CDC class C event within the past 12 months.
• Renal disease (as defined by estimated creatinine clearance less than 50 mL/min/1.73m2 confirmed on two occasions within 3 months of screening).
• Active opportunistic infections, including active tuberculosis (TB).
• Current treatment for active systemic TB. If recent, infection must have completed treatment course. INH treatment for latent TB is allowed.
• Viral load greater than 250,000 copies/mL at screening.
• Known greater than or equal than Grade 3 of any of the following laboratory toxicities within 30 days prior to study entry: neutrophil count, hemoglobin, platelets, AST, ALT, lipase, serum creatinine. Note: Subjects could be re-screened and enrolled if repeat value was less than Grade 3 without signs or symptoms of related organ dysfunction.
• Known greater than or equal to Grade 4 laboratory toxicities within 30 days prior to study entry, except with approval of the study team.
• For subjects who were not taking 3TC or FTC at the time of screening: Documented prior intolerance or adverse effect reasonably attributed to 3TC or FTC that resulted in permanent discontinuation.
• Problems with non-adherence attributed to modifiable structural barriers, such as lack of resources (e.g., insurance, transportation).
• Met requirements for completion of Step 1

Sponsors & Collaborators

• International Maternal Pediatric Adolescent AIDS Clinical Trials Group: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (17)

Univ. of California San Francisco NICHD CRS (5091)

San Francisco, California, 94117, United States

Location

Children's National Med. Ctr. Washington DC NICHD CRS (5015)

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida (5051)

Jacksonville, Florida, 32209, United States

Location

Univ of Miami Pediatric/Perinatal HIV/AIDS (4201)

Miami, Florida, 33136, United States

Location

Chicago Children's CRS (4001)

Chicago, Illinois, 60614, United States

Location

Johns Hopkins University NICHD CRS (5092)

Baltimore, Maryland, 21287, United States

Location

Metropolitan Hospital (5003)

New York, New York, 10029, United States

Location

SUNY Stony Brook NICHD CRS (5040)

Stony Brook, New York, 11794, United States

Location

Bronx-Lebanon Hospital (6901)

The Bronx, New York, 10457, United States

Location

DUMC Ped. CRS (4701)

Durham, North Carolina, 27710-3499, United States

Location

Hospital General de Agudos Buenos Aires Argentina NICHD CRS (5082)

Buenos Aires, C1221ADC, Argentina

Location

Hospital Geral De Nova Igaucu Brazil NICHD CRS (5097)

Rio de Janeiro, Rio de Janeiro, 26030, Brazil

Location

Insituto de Infectologia Emilio Ribas NICHD CRS (5075)

São Paulo, 01246-900, Brazil

Location

Univ of Sao Paulo Brazil NICHD CRS (5074)

São Paulo, 14049-900, Brazil

Location

University of Puerto Rico Pediatric HIV/AIDS Research (6601)

San Juan, 00936-5067, Puerto Rico

Location

Siriraj Hospital Mahidol University CRS (8251)

Bangkok, Ratchathewi,, 10700, Thailand

Location

Chiang Mai University Pediatrics-Obstetrics CRS (20101)

Chiang Mai, 50200, Thailand

Location

Related Publications (1)

• Agwu AL, Warshaw MG, McFarland EJ, Siberry GK, Melvin AJ, Wiznia AA, Fairlie L, Boyd S, Harding P, Spiegel HML, Abrams EJ, Carey VJ; P1094 Study Team. Decline in CD4 T lymphocytes with monotherapy bridging strategy for non-adherent adolescents living with HIV infection: Results of the IMPAACT P1094 randomized trial. PLoS One. 2017 Jun 12;12(6):e0178075. doi: 10.1371/journal.pone.0178075. eCollection 2017.

  PMID: 28604824 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Lamivudine; Emtricitabine; Racivir

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Results Point of Contact

• Title: Melissa Allen, Director, IMPAACT Operations Center
• Organization: Family Health International (FHI 360)

mallen@fhi360.org

(919) 405-1429

Study Officials

• Allison L. Agwu, MD, Sc.M.

  Johns Hopkins University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2011
• First Posted: April 19, 2011
• Study Start: March 1, 2011
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: November 13, 2015
• Results First Posted: May 23, 2014

Record last verified: 2015-10

Locations

PR (1); BR (3); TH (2); AR (1); US (10)