Addition of Raltegravir to Established Antiretroviral Suppressive Therapy

NCT01245101 | Terminated Phase 4 Results

• 1 other identifier: 20100499
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine whether intensification with raltegravir of a suppressive antiretroviral regimen in HIV infected patients with poor immune restoration has a beneficial effect on cryptic viral replication and the immune system. Specifically, the investigators will examine the effect that raltegravir intensification of ART has on episomal cDNA frequencies, immune activation, CD4+ cell counts and apoptosis, and markers of microbial translocation.

Conditions

HIV

Keywords

HIV raltegravir intensification replication activation

Outcome Measures

Primary Outcomes (1)

• Episomal HIV cDNA Formation

  These are linear viral cDNAs that are subsequently circularized by the DNA repair apparatus of the host cell to form episomes. They are markers of ongoing viral replication.

  16 weeks

Secondary Outcomes (1)

• Markers of Immune Activation

  16 weeks

Study Arms (2)

Raltegravir and then Observation

EXPERIMENTAL

The total duration of the study will be 40 weeks. This will include Part 1 (16 weeks) followed by Part 2 (8 weeks) followed by the crossover to Part 2 (16 weeks). During Part 1 participants in Group A will receive open-label raltegravir in addition to their established antiretroviral regimen while Group B participants will continue taking their established antiretroviral regimen for 16 weeks. After completion of Part 1, both groups will enter Part 2 that will consist of a washout period of 8 weeks during which both groups will only take their established antiretroviral regimen without raltegravir. This will be followed by Part 3 during which the two study groups will undergo a crossover with respect to the treatment assignment during Part 1 so that Group A will continue to receive their established antiretroviral regimen while Group B will receive open-label raltegravir in addition to their established antiretroviral regimen for 16 weeks.

Drug: Raltegravir

Observation and then Raltegravir

ACTIVE COMPARATOR

The total duration of the study will be 40 weeks. This will include Part 1 (16 weeks) followed by Part 2 (8 weeks) followed by the crossover to Part 2 (16 weeks). During Part 1 participants in Group A will receive open-label raltegravir in addition to their established antiretroviral regimen while Group B participants will continue taking their established antiretroviral regimen for 16 weeks. After completion of Part 1, both groups will enter Part 2 that will consist of a washout period of 8 weeks during which both groups will only take their established antiretroviral regimen without raltegravir. This will be followed by Part 3 during which the two study groups will undergo a crossover with respect to the treatment assignment during Part 1 so that Group A will continue to receive their established antiretroviral regimen while Group B will receive open-label raltegravir in addition to their established antiretroviral regimen for 16 weeks.

Drug: Raltegravir

Interventions

Raltegravir DRUG

Raltegravir 400 mg twice daily in addition to subject's antiretroviral therapy.

Raltegravir and then Observation

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To qualify for this study, participants will need to have:
• At least 18 years of age
• Documented HIV-1 infection
• CD4+ count \<350 cells/mm3 at the time of enrollment or CD4+ count increase of \<100 cells/mm3 within the past 2 years
• Plasma viral load \<400 copies/ml at all testing time points within the preceding 2 years AND \<50 copies/ml by RT-PCR or \<75 copies/ml by bDNA at the 2 testing time points immediately preceding enrollment into the study

You may not qualify if:

• Pregnancy or breast-feeding
• Prior use of raltegravir at any time in the past
• Use of any investigational, immunomodulatory, immunosuppressive agents within 90 days prior or during this study
• Alcohol or substance abuse that in the opinion of the investigator might interfere with patient compliance or safety
• Any condition or pre-study laboratory abnormality that in the opinion of the investigator might interfere with patient compliance or safety

Sponsors & Collaborators

• University of Miami: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Infectious Diseases Research Unit, University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

MeSH Terms

Interventions

Raltegravir Potassium

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Only 11 of 12 patients completed week 40 and were analyzed as per protocol. In view of poor enrollment and a simple analysis of the limited amount of data that failed to support our hypothesis, the study was terminated early.

Results Point of Contact

• Title: Rafael E. Campo
• Organization: University of Miami

rcampo@med.miami.edu

305-689-7030

Study Officials

• Rafael E Campo, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Clinical

Study Record Dates

• First Submitted: November 19, 2010
• First Posted: November 22, 2010
• Study Start: November 1, 2010
• Primary Completion: October 1, 2012
• Study Completion: May 1, 2013
• Last Updated: December 23, 2016
• Results First Posted: December 23, 2016

Record last verified: 2016-10

Locations

US (1)