Switch From Tenofovir to Raltegravir for Low Bone Mineral Density (TROP)

The purpose of this study is to determine if low bone mineral density (a measurement of how thick and strong bones are) improves in adults with HIV infection who switch their HIV medication tenofovir to another HIV medication raltegravir.

Hypothesis:That Bone Mineral Density (BMD) will improve in osteopenic or osteoporotic patients switching from ART including tenofovir disoproxil fumarate (TDF) and a ritonavir-boosted protease inhibitor (r/PI) to ART including RAL+r/PI.

Study Overview

• Status: Completed
• Conditions: HIV Infections; HIV; Osteoporosis; Osteopenia
• Intervention / Treatment: Drug: Raltegravir

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2010
      • St Vincents Hospital
    • Sydney, New South Wales, Australia, 2010
      • East Sydney Doctors
    • Sydney, New South Wales, Australia, 2010
      • Holdsworth Medical Practice
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. provision of written, informed consent
2. HIV-infected adults at least 18 years of age
3. receiving stable ART including TDF and a r/PI for the previous 6 months
4. no prior PI genotypic resistance or known replication of HIV in patients receiving a PI
5. plasma HIV RNA < 50 copies/ml for at least the previous 3 months

6. spine or neck of femur t-score ≤ -1.0 (i.e. WHO-defined osteopenia) measured by dual energy x-ray absorptiometry (DEXA)

   Exclusion Criteria:

7. participation in any other clinical trial (unless approved by the study PI)
8. use of TDF for previously active chronic hepatitis B infection
9. receiving or requiring therapy for low BMD (including prior fragility fracture)
10. using oral corticosteroids or inhaled fluticasone
11. virological failure on, or intolerance to, RAL
12. contra-indication to RAL therapy (see appendix 2)
13. breast-feeding
14. pregnancy
15. secondary, endocrinological cause of low BMD:25-hydroxy vitamin D deficiency, hypogonadism: a)symptomatic b)asymptomatic defined by total testosterone > 25% below lower limit of reference range and/or luteinizing hormone > 2 x upper limit of normal (ULN),untreated hypothyroidism or hyperparathyroidism according to local reference ranges

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Raltegravir	Drug: Raltegravir; Raltegravir tablet 400mg is taken orally, twice daily with or without food for 48 weeks.; Other Names: Isentress; MK-0518

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Bone Mineral Density (BMD) of Lumbar Spine and Hips	Percent Change in Bone Mineral Density of Lumbar Spine and Hips from Baseline to Weeks 48 and 96	from Baseline to Weeks 48 and 96

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV Viral Load <50 Copies/mL	Plasma HIV viral load remained <50 copies/mL	from Baseline to Week 96

Collaborators and Investigators

• Sponsor: St Vincent's Hospital, Sydney
• Collaborators: Merck Sharp & Dohme LLC; The Alfred; Holdsworth House Medical Practice
• Investigators: Principal Investigator: Andrew D Carr, Professor, St Vincents Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: July 14, 2009
• First Submitted That Met QC Criteria: July 14, 2009
• First Posted (Estimate): July 15, 2009

Study Record Updates

• Last Update Posted (Estimate): June 12, 2015
• Last Update Submitted That Met QC Criteria: May 28, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: osteoporosis; Tenofovir; treatment experienced; osteopenia; Raltegravir; bone markers; HIV+
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Osteoporosis; Bone Diseases, Metabolic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Raltegravir Potassium
• Other Study ID Numbers: TROP