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Multicentre Study To Assess Changes In Bone Mineral Density Of The Switch From Protease Inhibitors To Dolutegravir In HIV-1-Infected Subjects With Low Bone Mineral Density

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Fundacio Lluita Contra la SIDA
Sponsor:
Information provided by (Responsible Party):
Fundacio Lluita Contra la SIDA
ClinicalTrials.gov Identifier:
NCT01966822
First received: October 7, 2013
Last updated: October 13, 2014
Last verified: October 2014

October 7, 2013
October 13, 2014
January 2014
October 2015   (final data collection date for primary outcome measure)
  • Compare changes in Bone Mineral Density (BMO) measured by Dual-energy X-ray absorptiometry [ Time Frame: From Baseline to week 48 ] [ Designated as safety issue: Yes ]
  • Compare changes in femur T-score measured by DEXA [ Time Frame: From Baseline to week 48 ] [ Designated as safety issue: Yes ]
  • Compare changes in lumbar spine (L1-L4) T-score measured by DEXA [ Time Frame: From Baseline to week 48 ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01966822 on ClinicalTrials.gov Archive Site
  • HIV-1 viral load [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • HIV-1 viral load [ Time Frame: week 4 ] [ Designated as safety issue: No ]
  • HIV-1 viral load [ Time Frame: week 12 ] [ Designated as safety issue: No ]
  • HIV-1 viral load [ Time Frame: week 24 ] [ Designated as safety issue: No ]
  • HIV-1 viral load [ Time Frame: week 48 ] [ Designated as safety issue: No ]
  • CD4+/CD8+ T lymphocytes count. [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • CD4+/CD8+ T lymphocytes count. [ Time Frame: week 4 ] [ Designated as safety issue: No ]
  • CD4+/CD8+ T lymphocytes count. [ Time Frame: week 12 ] [ Designated as safety issue: No ]
  • CD4+/CD8+ T lymphocytes count. [ Time Frame: week 24 ] [ Designated as safety issue: No ]
  • CD4+/CD8+ T lymphocytes count. [ Time Frame: week 48 ] [ Designated as safety issue: No ]
  • Genotypic test if virological failure occurs. [ Time Frame: From baseline to week 48 ] [ Designated as safety issue: No ]
  • Compare changes in total cholesterol [ Time Frame: at week 48 relative to baseline values ] [ Designated as safety issue: Yes ]
  • Compare changes in HDL cholesterol [ Time Frame: at week 48 relative to baseline values ] [ Designated as safety issue: Yes ]
  • Compare changes in LDL cholesterol [ Time Frame: at week 48 relative to baseline values ] [ Designated as safety issue: Yes ]
  • Compare changes in triglyceride levels. [ Time Frame: at week 48 relative to baseline values ] [ Designated as safety issue: Yes ]
  • Compare changes in filtrate glomerular rate by MDRD equation [ Time Frame: at week 48 relative to baseline values ] [ Designated as safety issue: Yes ]
  • Compare changes in creatinine [ Time Frame: at week 48 relative to baseline values ] [ Designated as safety issue: Yes ]
  • Compare changes in albumine/creatinine ratio [ Time Frame: at week 48 relative to baseline values ] [ Designated as safety issue: Yes ]
  • Compare changes in proteinuria/creatinine ratio [ Time Frame: at week 48 relative to baseline values ] [ Designated as safety issue: Yes ]
  • Adverse events related to antiretroviral treatment (Toxicity). [ Time Frame: From Baseline to week 48 ] [ Designated as safety issue: Yes ]
  • Patient withdrawal [ Time Frame: From Baseline to week 48 ] [ Designated as safety issue: Yes ]
  • Compare changes in osteocalcin [ Time Frame: at week 48 relative to baseline values ] [ Designated as safety issue: Yes ]
  • Compare changes in alkaline phosphatase [ Time Frame: at week 48 relative to baseline values ] [ Designated as safety issue: Yes ]
  • Compare changes in telopeptide [ Time Frame: at week 48 relative to baseline values ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Multicentre Study To Assess Changes In Bone Mineral Density Of The Switch From Protease Inhibitors To Dolutegravir In HIV-1-Infected Subjects With Low Bone Mineral Density
MULTICENTRE STUDY TO ASSESS CHANGES IN BONE MINERAL DENSITY OF THE SWITCH FROM PROTEASE INHIBITORS TO DOLUTEGRAVIR IN HIV-1-INFECTED SUBJECTS WITH LOW BONE MINERAL DENSITY

Protease inhibitors (PI) have been associated with an acceleration of bone mineral density loss in HIV-infected individuals because of an enhanced osteoclast activity, although some controversial data have been also published. A first study suggest an increase of bone mineral density after switching from PI to raltegravir, the first generation integrase inhibitor, but there are no more data about this subject.

Based on data that PI decrease bone mineral density by accelerating osteoclast cells and that the discontinuation of this drugs could improve bone mineralization, we propose a randomized prospective multicenter study to assess the impact of switching from PI to dolutegravir on bone mineral density in patients with low bone mineral density receiving a PI-containing regimen. At the same time, the study will help to assess the antiviral efficacy and safety of a PI-sparing regimen including dolutegravir as a simplification strategy in virologically suppressed patients.

The second generation integrase inhibitor dolutegravir has demonstrated good virological and immunological outcomes in antiretroviral-naive subjects, compared with efavirenz, (SPRING 1 study). As well, it is active against HIV strains resistant to first-generation inhibitors raltegravir and elvitegravir in heavily treatment-experienced patients (VIKING study).

Additionally, it was safe and well tolerated after two years of use. It is administered once daily with no need for boosting, no food requirements and has a long half-life. The easy posology and its pharmacokinetics, together with the antiviral potency, make this drug a good alternative as a simplification approach. However, no clinical data are available supporting the switch of protease inhibitors or no nucleoside reverse transcriptase inhibitors to dolutegravir in virologically suppressed HIV-treated subjects.

Protease inhibitors (PI) have been associated with an acceleration of bone mineral density loss in HIV-infected individuals because of an enhanced osteoclast activity, although some controversial data have been also published. A first study suggest an increase of bone mineral density after switching from PI to raltegravir, the first generation integrase inhibitor, but there are no more data about this subject.

Based on data that PI decrease bone mineral density by accelerating osteoclast cells and that the discontinuation of this drugs could improve bone mineralization, we propose a randomized prospective multicenter study to assess the impact of switching from PI to dolutegravir on bone mineral density in patients with low bone mineral density receiving a PI-containing regimen. At the same time, the study will help to assess the antiviral efficacy and safety of a PI-sparing regimen including dolutegravir as a simplification strategy in virologically suppressed patients.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV-1 Infection
  • Drug: Dolutegravir, 50mg every 24 hours
    Dolutegravir, 50mg every 24 hours
  • Drug: Protease Inhibitor/ritonavir
    Protease Inhibitor/ritonavir
  • Experimental: Dolutegravir 50mg
    Dolutegravir 50mg every 24 hours + Kivexa (ABC+3TC)
    Intervention: Drug: Dolutegravir, 50mg every 24 hours
  • Active Comparator: Protease Inhibitor/ritonavir
    Protease Inhibitor/ritonavir + Kivexa (ABC+3TC)
    Intervention: Drug: Protease Inhibitor/ritonavir
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
80
October 2015
October 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. HIV-infected patients over 18 years.
  2. In current antiretroviral therapy with abacavir and lamivudine (Kivexa) plus ritonavir-boosted PI, at least 6 months.
  3. Viral suppression (HIV RNA <50 copies / ml) for at least 12 months.
  4. T-score ≤ -1 evaluated by DEXA (done in the last 6 months).
  5. Signed informed consent.
  6. In potential childbearing women, commitment to use barrier contraceptive method throughout the study.

Exclusion Criteria:

  1. Suspected or documented resistance to integrase inhibitors or reverse transcriptase inhibitors, nucleoside analogues.
  2. Osteoporosis / osteopenia secondary (testosterone deficiency, thyroid disease ...), except vitamin D deficiency
  3. Treatment with bisphosphonates in the last 6 months.
  4. Have used integrase inhibitors
  5. Pregnant or breastfeeding.
  6. Patients with alanine aminotransferase (ALT)> 5 times the upper limit of normal (ULN) or ALT ≥ 3 times ULN and bilirubin ≥ 1.5 times ULN (direct bilirubin> 35%)
  7. Patients with severe hepatic dysfunction (Class B or C) according to the Child-Pugh classification
  8. Patients infected with hepatitis B virus (HBV) who can not use entecavir or telbivudine.
  9. Patients infected with hepatitis C virus (HCV) in which is expected to begin treatment during the study.
Both
18 Years to 65 Years
No
Contact: Negredo Eugènia, Md,PhD 0034936457897 enegredo@flsida.org
Spain
 
NCT01966822
OSTEODOLU
No
Fundacio Lluita Contra la SIDA
Fundacio Lluita Contra la SIDA
Not Provided
Not Provided
Fundacio Lluita Contra la SIDA
October 2014

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