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Second-line Switch to Dolutegravir Study (2SD)

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ClinicalTrials.gov Identifier: NCT04229290
Recruitment Status : Not yet recruiting
First Posted : January 18, 2020
Last Update Posted : January 28, 2020
Sponsor:
Collaborator:
ViiV Healthcare
Information provided by (Responsible Party):
Loice Achieng, University of Nairobi

Brief Summary:

Kenya has the 4th largest HIV burden in the world with about 1.6 million people living with HIV. Of these, just over 1 million are on antiretroviral therapy (ART). Current national guidelines recommend a first line regimen composed of 2 nucleoside reverse transcriptase inhibitors (NRTI) plus an integrase strand transfer inhibitor (INSTI) or a non-nucleoside reverse transcriptase inhibitor(NNRTI). Second line regimens are composed of 2 NRTI plus a ritonavir boosted protease inhibitor(PIr). This is based on evidence showing good clinical outcomes on this regimen. PIr are associated with side effects including an increase in cardiovascular disease risk and, have significant drug to drug interactions that complicate management of other conditions such as tuberculosis. INSTIs have been shown in one study to be an alternative to PIr in second line regimens when combined with fully active NRTIs. It is not clear if this would still be the case if the activity of the NRTIs was not known. The investigators will evaluate the efficacy of switching from a PIr to a dolutegravir based second line ART regimen.

Hypothesis: switching virologically suppressed patients from a PIr based second line to a dolutegravir based second line is non-inferior to continuing on a PIr based second line.

Objectives: The primary objective will be to evaluate the non-inferiority of switching to a DTG containing regimen relative to maintaining a PI/r containing second-line regimen in virologically suppressed, INSTI-naive HIV-1 positive adults (≥ 18 years old) as determined by having HIV-1 RNA ≥ 50 copies/ml at week 48. Secondary objectives will be to assess the impact of such a switch on CD4 count, safety and tolerability.

Methods: Open-label, randomized, non-inferiority, multisite trial over 48 weeks, describing the efficacy and safety of switching from a second-line ARV regimen containing a ritonavir-boosted protease inhibitor (PI/r) plus 2 NRTIs to DTG plus 2 NRTIs in patients with virological suppression (HIV-1 RNA < 50 copies/ml) for at least 12 weeks and with no prior INSTI exposure. Adult participants will be randomized at baseline to remain on their pre-enrollment PI/r or switch to DTG. Participants will continue the NRTIs from their pre-enrollment regimen in both arms. A total of 766 participants(388 per arm) will be recruited from 4 sites in Kenya Conclusion: This study seeks to inform guidelines around the efficacy and safety of alternative second line regimens.


Condition or disease Intervention/treatment Phase
HIV-1-infection Drug: Dolutegravir Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 766 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomised controlled, open label clinical trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Switching Treatment-Experienced, Integrase Inhibitor-Naïve, Virally Suppressed HIV-1 Infected Adults From Ritonavir Boosted Protease Inhibitors to Dolutegravir: An Open-Label Randomized Controlled Trial
Estimated Study Start Date : January 20, 2020
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : July 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Dolutegravir
Participants in this arm will have a switch from a protease inhibitor based second line regimen to Dolutegravir maintaining the same NRTI backbone
Drug: Dolutegravir
Switch of virally suppressed participants to Dolutegravir
Other Name: DTG

Active Comparator: Protease Inhibitor
Participants in this arm will be maintained on their protease inhibitor based second line regimen
Drug: Dolutegravir
Switch of virally suppressed participants to Dolutegravir
Other Name: DTG




Primary Outcome Measures :
  1. Virologic failure [ Time Frame: 48 weeks ]
    Proportion of participants with HIV-1 RNA ≥ 50 copies/ml at week 48 (by US Food and Drug Administration snapshot algorithm, modified to allow for changes in NRTIs for clinical reasons)


Secondary Outcome Measures :
  1. Virologic failure [ Time Frame: 24 weeks ]
    Proportion of participants with HIV-1 RNA ≥ 50 copies/ml at week 24

  2. Treatment success [ Time Frame: 24 and 48 weeks ]
    Proportion of participants able to maintain virological suppression (HIV-1 RNA < 50 copies/ml with no discontinuation of the study treatment)

  3. CD4 count [ Time Frame: 24 and 48 weeks ]
    Change in CD4 count from baseline

  4. Weight [ Time Frame: 24 and 48 weeks ]
    Change in body weight from baseline

  5. Body mass index [ Time Frame: 24 and 48 weeks ]
    Change in body mass index from baseline

  6. Waist-hip ratio [ Time Frame: 24 and 48 weeks ]
    Change in waist-hip ratio from baseline

  7. Waist circumference [ Time Frame: 24 and 48 weeks ]
    Change in waist circumference from baseline

  8. Blood sugar [ Time Frame: 24 and 48 weeks ]
    Change in blood sugar from baseline

  9. Total cholesterol [ Time Frame: 24 and 48 weeks ]
    Change in blood total cholesterol from baseline

  10. Low density lipoprotein [ Time Frame: 24 and 48 weeks ]
    Change in low density lipoprotein from baseline

  11. Triglyceride [ Time Frame: 24 and 48 weeks ]
    Change in triglyceride from baseline

  12. Total cholesterol:HDL ratio [ Time Frame: 24 and 48 weeks ]
    Change in total cholesterol:HDL ratio from baseline

  13. Percentage of participants experiencing an adverse event [ Time Frame: 24 and 48 weeks ]
    clinical and laboratory adverse events

  14. Resistance [ Time Frame: 48 weeks ]
    Genotypic resistance mutations for participants with protocol-defined virological failure

  15. Patient satisfaction: HIV Treatment Satisfaction Questionnaire scores [ Time Frame: Baseline, week 24 and week 48 ]
    HIV Treatment Satisfaction Questionnaire scores. Scores range from 0-60 with higher scores reflecting greater satisfaction with treatment



Information from the National Library of Medicine

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

Inclusion Criteria:

  • Able and willing to understand and comply with the protocol requirements, instructions and restrictions
  • Able and willing to give informed consent
  • Age 18 years or above
  • Documented HIV-1 infection as confirmed by HIV-antibody testing as per the Kenya National Guidelines
  • Has been receiving a second-line ARV regimen containing a PI/r (DRV/r, ATV/r or LPV/r) and 2 NRTIs for at least 24 weeks
  • Documented HIV-1 RNA viral load < 50 copies/ml at least 12 weeks prior to enrollment and no viral rebound between the first viral load < 50 copies/ml and the screening viral load
  • HIV-1 RNA viral load < 50 copies/ml at screening (within 28 days prior to enrollment)
  • If female and of childbearing potential, is using effective contraception and is willing to continue using effective contraception throughout the study period (as defined in Appendix 5). Note: Non-childbearing potential is defined as either post-menopausal (12 months of spontaneous amenorrhoea and age of 45 years or above) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy

Exclusion Criteria:

  • Any prior use of integrase inhibitor
  • Documented HIV-2 infection
  • Using any concomitant therapy disallowed as per the reference safety information and product labelling for the study drugs
  • Has AST and/or ALT at least 5-times greater than the upper limit of normal in conjunction with hepatitis B virus infection (HBV) or hepatitis C virus infection (HCV). Note: patients can enter the study with chronic HBV or HCV if AST and ALT are less than 5-times greater than the upper limit of normal and, in the investigators opinion, their medical status will not interfere with assessments or completion of the study
  • Is both HBsAg positive and has a CrCl below 50 ml/min (as estimated using the Cockcroft-Gault estimate for glomerular filtration rate)
  • Advanced renal insufficiency requiring dialysis
  • If female, currently pregnant or breastfeeding, or intending to become pregnant during the study period
  • Documented opportunistic infection within 4 weeks prior to the study enrolment
  • Investigator opinion that the patient should switch from PI/r to DTG immediately for clinical reasons
  • Any condition (including illicit drug use or alcohol abuse) or laboratory results which, in the investigator's opinion, interfere with assessments or completion of the study
  • History or presence of allergy to the study drugs or their components

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04229290


Contacts
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Contact: Joseph Nkuranga, MBChB, MPH +254 737 223988 joseph.nku@gmail.com

Locations
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Kenya
Kiambu Level 5 Hospital
Kiambu, Kenya
Contact: Joseph Nkuranga, MBChB, MPH    +254 737 223988    joseph.nku@gmail.com   
Sub-Investigator: Jared Mecha, MD, MSC         
Jaramogi Oginga Odinga Teaching and Referral Hospital
Kisumu, Kenya
Contact: Joseph Nkuranga, MBChB, MPH    +254 737 223988    joseph.nku@gmil.com   
Sub-Investigator: Florentius Ndinya, MBChB MMED         
Sub-Investigator: Rukia Aksam, MBChB         
Kenyatta National Hospital
Nairobi, Kenya
Contact: Joseph Nkuranga, MBChB, MPH    +254 737 223988    joseph.nku@gmail.com   
Principal Investigator: Loice Achieng, MD, MSC         
Principal Investigator: Jeremy Penner, MD         
Sub-Investigator: Peter Muiruri, MBChB, MPH         
Sub-Investigator: Mareen Kimani, MBChB, MPH         
Thika Level 5 Hospital
Thika, Kenya
Contact: Joseph Nkuranga, MBChB, MPH    +254 737 223988    joseph.nku@gmail.com   
Sub-Investigator: Jared Mecha, MD, MSC         
Sponsors and Collaborators
University of Nairobi
ViiV Healthcare
Investigators
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Principal Investigator: Loice Achieng, MD, MSC University of Nairobi

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Responsible Party: Loice Achieng, Principal Investigator, University of Nairobi
ClinicalTrials.gov Identifier: NCT04229290    
Other Study ID Numbers: 2SD
First Posted: January 18, 2020    Key Record Dates
Last Update Posted: January 28, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: We will share IPD that underlie the results reported after de-identification (text, tables, figures and appendices)
Supporting Materials: Study Protocol
Time Frame: Beginning 6 months after article publication and for a period of 36 months
Access Criteria: Researchers that provide a methodologically sound proposal and whose proposal has been approved by an independent review committee

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Loice Achieng, University of Nairobi:
HIV
Second-line
Switch
Protease inhibitor
Dolutegravir
Treatment experienced
Non-inferiority
Additional relevant MeSH terms:
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HIV Protease Inhibitors
Dolutegravir
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
HIV Integrase Inhibitors
Integrase Inhibitors