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HIV-1 InfectionPhase 3NCT01966822

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

A Phase 3 study testing Dolutegravir, 50mg every 24 hours and Protease Inhibitor/ritonavir in people with HIV-1 Infection, run by Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia at 3 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
HIV-1 Infection
What is being tested?
Dolutegravir, 50mg every 24 hours and Protease Inhibitor/ritonavir
Could I receive a placebo?
No, everyone receives an active treatment
How many people
75 participants
Where
3 sitesSpain
Study dates
Jan 2014to Oct 2015
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • Suspected or documented resistance to integrase inhibitors or reverse transcriptase inhibitors, nucleoside analogues.
  • Osteoporosis / osteopenia secondary (testosterone deficiency, thyroid disease ...), except vitamin D deficiency
  • Treatment with bisphosphonates in the last 6 months.
  • Have used integrase inhibitors
  • Pregnant or breastfeeding.
  • 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%)
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  • Patients with severe hepatic dysfunction (Class B or C) according to the Child-Pugh classification
  • Patients infected with hepatitis B virus (HBV) who can not use entecavir or telbivudine.
  • Patients infected with hepatitis C virus (HCV) in which is expected to begin treatment during the study.

Trial locations and contacts

3 sites in 1 country.

Spain3 sites

  • GermansTrias i Pujol Hospital

    Badalona, Barcelona, 08916

  • Hospital de la Santa Creu i Sant Pau

    Barcelona, Barcelona, 08025

  • Hospital Clínico San Carlos

    Madrid, Madrid, 28040

Other trials in Spain

About this study

Official title: 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.

Read the detailed description

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.

Conditions
HIV-1 Infection
Being tested
Dolutegravir, 50mg every 24 hours, Protease Inhibitor/ritonavir
Keywords
Osteoporosis, Bone mineral density, Dual-energy X-ray absorptiometry, HIV infection, Dolutegravir, Integrase inhibitor
Medical subject headings
Osteoporosis, HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dolutegravir, 50mg every 24 hoursDrug

    Dolutegravir, 50mg every 24 hours

  • Protease Inhibitor/ritonavirDrug

    Protease Inhibitor/ritonavir

Study groups in NCT01966822
Study groupRoleWhat they receive
Dolutegravir 50mgExperimentalDolutegravir 50mg every 24 hours + Kivexa (ABC+3TC)
Receives: Drug: Dolutegravir, 50mg every 24 hours
Protease Inhibitor/ritonavirActive comparatorProtease Inhibitor/ritonavir + Kivexa (ABC+3TC)
Receives: Drug: Protease Inhibitor/ritonavir

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Compare changes in Bone Mineral Density (BMO) measured by Dual-energy X-ray absorptiometry

    Measured: From Baseline to week 48

  2. Compare changes in femur T-score measured by DEXA

    Measured: From Baseline to week 48

  3. Compare changes in lumbar spine (L1-L4) T-score measured by DEXA

    Measured: From Baseline to week 48

Secondary outcomes (24)

  1. HIV-1 viral load

    Measured: Baseline

  2. HIV-1 viral load

    Measured: week 4

  3. HIV-1 viral load

    Measured: week 12

  4. HIV-1 viral load

    Measured: week 24

  5. HIV-1 viral load

    Measured: week 48

  6. CD4+/CD8+ T lymphocytes count.

    Measured: Baseline

  7. CD4+/CD8+ T lymphocytes count.

    Measured: week 4

  8. CD4+/CD8+ T lymphocytes count.

    Measured: week 12

  9. CD4+/CD8+ T lymphocytes count.

    Measured: week 24

  10. CD4+/CD8+ T lymphocytes count.

    Measured: week 48

  11. Genotypic test if virological failure occurs.

    Measured: From baseline to week 48

  12. Compare changes in total cholesterol

    Measured: at week 48 relative to baseline values

  13. Compare changes in HDL cholesterol

    Measured: at week 48 relative to baseline values

  14. Compare changes in LDL cholesterol

    Measured: at week 48 relative to baseline values

  15. Compare changes in triglyceride levels.

    Measured: at week 48 relative to baseline values

  16. Compare changes in filtrate glomerular rate by MDRD equation

    Measured: at week 48 relative to baseline values

  17. Compare changes in creatinine

    Measured: at week 48 relative to baseline values

  18. Compare changes in albumine/creatinine ratio

    Measured: at week 48 relative to baseline values

  19. Compare changes in proteinuria/creatinine ratio

    Measured: at week 48 relative to baseline values

  20. Adverse events related to antiretroviral treatment (Toxicity).

    Measured: From Baseline to week 48

  21. Patient withdrawal

    Measured: From Baseline to week 48

  22. Compare changes in osteocalcin

    Measured: at week 48 relative to baseline values

  23. Compare changes in alkaline phosphatase

    Measured: at week 48 relative to baseline values

  24. Compare changes in telopeptide

    Measured: at week 48 relative to baseline values

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Oct 2013 (estimated)
  2. Study startJan 2014
  3. Primary completionOct 2015
  4. Study completionOct 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
75 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01966822
Sponsor's protocol ID
OSTEODOLU
Status last verified
Nov 2015
First submitted
7 Oct 2013
Last updated
30 Nov 2015
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Dolutegravir, 50mg every 24 hours and Protease Inhibitor/ritonavir in people with HIV-1 Infection, run by Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia at 3 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Compare changes in Bone Mineral Density (BMO) measured by Dual-energy X-ray absorptiometry (time frame: From Baseline to week 48). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01966822.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Nov 2015.

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