This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

Dolutegravir Antiretroviral Strategy to Promote Improvement and Reduce Drug Exposure (ASPIRE)

This study has been completed.
Sponsor:
Collaborator:
ViiV Healthcare
Information provided by (Responsible Party):
Babafemi Taiwo, Northwestern University
ClinicalTrials.gov Identifier:
NCT02263326
First received: October 6, 2014
Last updated: September 12, 2017
Last verified: September 2017
  Purpose
HIV-1 infected subjects with CD4 nadir > 200 cells/mm3, no history of virologic failure and plasma HIV RNA <50 copies/mL for at least 48 weeks while on any United States Department of Health and Human Services (DHHS) recommended or alternative three-drug antiretroviral regimen will be randomized to dolutegravir (DTG) plus lamivudine (Arm 1) or continuation of their current regimen (Arm 2) for 48 weeks. The primary endpoint is virologic failure defined as confirmed plasma HIV-1 RNA > 50 copies/mL before or at Week 24

Condition Intervention Phase
HIV Infection Drug: dolutegravir Drug: lamivudine Drug: Continue current antiretroviral regimen Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Dolutegravir Antiretroviral Strategy to Promote Improvement and Reduce Drug Exposure (ASPIRE) Study

Resource links provided by NLM:


Further study details as provided by Babafemi Taiwo, Northwestern University:

Primary Outcome Measures:
  • Virologic failure rate [ Time Frame: 24 weeks ]
    Rate of virologic failure (confirmed HIV RNA >50 copies/mL) between those who continue their current ART regimen and those who switch to DTG + lamivudine


Secondary Outcome Measures:
  • CD4 count [ Time Frame: 48 weeks ]
    Impact of switching on CD4 count

  • Rates of HIV-1 viremia [ Time Frame: 48 weeks ]
    Rates of HIV-1 viremia (>20, >50, >200)

  • Clinical and laboratory toxicities [ Time Frame: 48 weeks ]
    Number of Grade 3 or above clinical and laboratory toxicities assessed at each study visit

  • HIV-1 detection by single-copy assay [ Time Frame: 48 weeks ]
    Change in HIV-1 detection by the HIV-1 single copy assay

  • Drug resistance associated mutations [ Time Frame: 48 weeks ]
    Drug resistance mutations measured by HIV genotyping in patients with confirmed virologic failure

  • Adherence [ Time Frame: 48 weeks ]
    adherence measure by self-report of missed doses


Enrollment: 90
Study Start Date: December 2014
Study Completion Date: September 2017
Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: dolutegravir plus lamivudine
dolutegravir 50 mg plus lamivudine 300 mg once daily
Drug: dolutegravir
50 mg tablet by mouth once daily for 48 weeks
Other Name: TIVICAY, DTG
Drug: lamivudine
300 mg tablet by mouth once daily for 48 weeks
Other Name: EPIVIR, 3TC
Active Comparator: Continue current ART regimen
Continue current DHHS recommended or alternative three-drug antiretroviral regimen
Drug: Continue current antiretroviral regimen
Continue current DHHS recommended or alternative three-drug antiretroviral regimen

Detailed Description:

DESIGN HIV-1 infected subjects with CD4 nadir > 200 cells/mm3, no history of virologic failure and plasma HIV RNA <50 copies/mL for at least 48 weeks while on any United States Department of Health and Human Services (DHHS) recommended or alternative three-drug antiretroviral regimen will be randomized to dolutegravir (DTG) plus lamivudine (Arm 1) or continuation of their current regimen (Arm 2) for 48 weeks. The primary endpoint is virologic failure defined as confirmed plasma HIV-1 RNA > 50 copies/mL before or at Week 24

All subjects will undergo routine monitoring including plasma HIV-1 RNA, CD4/CD8 count, hematology, chemistry and fasting lipids. Resistance testing will be done in all patients who experience virologic failure. Single-copy HIV-1 assay will be done to quantify residual viremia.

DURATION 48 weeks

SAMPLE SIZE 90 subjects

POPULATION HIV-1-infected men and women, 18 years and older, with CD4 nadir > 200 cells/mm3, no baseline resistance, no history of virologic failure, and HIV RNA <50 copies/mL for at least 48 weeks prior to study entry while on any DHHS recommended or alternative three-drug regimen

REGIMEN Subjects will be randomized (1:1) to:

Arm 1: dolutegravir 50 mg plus lamivudine 300 mg once daily OR Arm 2: Continue current DHHS recommended or alternative three-drug antiretroviral regimen

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 Infection
  • HIV-1 RNA <50 copies/mL on all measurements within 48 weeks prior to study entry while on any DHHS recommended or alternative three-drug antiretroviral regimen. (A history of switching for simplification and/or tolerability is allowed. At least two measurements within the previous 48 weeks are required prior to study screening.)
  • No history of virologic failure, defined as consecutive HIV RNA > 50 copies/mL after 12 months of initiating ART. An isolated (non-consecutive) HIV RNA > 50 copies/mL (but less than 400 copies/mL) is permitted after 12 months of initiating ART but not in the 48-week window prior to study entry.
  • Screening plasma HIV RNA < 20 copies/mL using the COBAS AmpliPrep/COBAS TaqMan HIV-1 Test V2.0, obtained within 45 days prior to study entry
  • Nadir CD4 count >200 cells/mm
  • Pretreatment genotype documenting no mutations in the protease or reverse transcriptase genes
  • No known resistance to integrase inhibitors
  • Laboratory values obtained within 45 days prior to study entry:

ANC >750 Hemoglobin >10 g/dL Platelets >50,000 Calculated creatinine clearance (CrCl) >50 mL/min

  • Negative serum or urine pregnancy test
  • Men and women age greater or equal to 18 years.
  • Ability to continue current regimen (i.e, have uninterrupted access)
  • No evidence of chronic hepatitis B

Exclusion Criteria:

  • Serious illness or AIDS-related complication within 21 days of screening requiring systemic treatment and/or hospitalization
  • Treatment within 30 days prior to study entry with immune modulators
  • Vaccination within 7 days
  • Active HCV treatment or anticipated need for treatment within study period. (HCV infection alone is not exclusionary)
  • Unstable liver disease or severe hepatic impairment
  • Known allergy or hypersensitivity to DTG or lamivudine.
  • Active drug or alcohol use or dependence that could interfere with adherence to study requirements
  • ALT (alanine aminotransferase) >5 x ULN (upper limit of normal) OR ALT >3 x ULN and total bilirubin >1.5 x ULN (with 35% direct bilirubin)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02263326

Locations
United States, California
University of California San Diego
San Diego, California, United States
United States, Georgia
Emory University
Atlanta, Georgia, United States
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States
United States, New York
Cornell University
New York, New York, United States
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States
The Ohio State University
Columbus, Ohio, United States
Sponsors and Collaborators
Babafemi Taiwo
ViiV Healthcare
Investigators
Principal Investigator: Babafemi Taiwo, MBBS Northwestern University
  More Information

Responsible Party: Babafemi Taiwo, Associate Professor, Northwestern University
ClinicalTrials.gov Identifier: NCT02263326     History of Changes
Other Study ID Numbers: ASPIRE
Study First Received: October 6, 2014
Last Updated: September 12, 2017

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Lamivudine
Dolutegravir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents
HIV Integrase Inhibitors
Integrase Inhibitors

ClinicalTrials.gov processed this record on September 21, 2017