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Dolutegravir in Pregnant HIV Mothers and Their Neonates (DolPHIN-2)

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ClinicalTrials.gov Identifier: NCT03249181
Recruitment Status : Recruiting
First Posted : August 15, 2017
Last Update Posted : February 16, 2018
Sponsor:
Collaborators:
UNITAID
University of Cape Town
Liverpool School of Tropical Medicine
Infectious Diseases Institute, Uganda
Radboud University
Information provided by (Responsible Party):
Catriona Waitt, University of Liverpool

Brief Summary:

To evaluate dolutegravir (DTG) efficacy in women who present with untreated HIV in late pregnancy.

An open-label, multi-centre randomised controlled trial of DTG vs efavirenz-based regimens for women commencing cART in late pregnancy. HIV positive pregnant women presenting with untreated HIV infection in late (≥28 weeks gestation) pregnancy will be randomised 1:1 to receive DTG (50mg once daily) + 2 nucleoside reverse transcriptase inhibitors (NRTIs) or EFV + 2 NRTIs (SoC)


Condition or disease Intervention/treatment Phase
HIV-1-infection Pregnancy Related Drug: Dolutegravir Drug: Standard of Care (EFV + 2 NRTI backbone) Phase 3

Detailed Description:

This is an open-label, randomised controlled trial of DTG versus EFV -based regimens for 250 women commencing cART in late pregnancy, randomised 1:1 to DTG vs EFV-based cART. The purpose of this study is to inform treatment guidelines and for the first time specifically address the treatment needs of this group of women- hence the trial is powered for superiority over EFV. The primary endpoints is maternal VL at delivery, with secondary endpoints including safety and tolerability of DTG in both mother and infant, VL decline in breast milk, development of drug resistance, pharmacokinetics of DTG in mother-infant pairs, pharmacogenomics factors relating to efficacy or toxicity of DTG, and MTCT of HIV up to 72 weeks postpartum. Two sites have been selected - Infectious Diseases Institute, Makerere University, Kampala, Uganda and the University of Cape Town, South Africa - both have a strong track record of successfully delivering collaborative multidisciplinary research in PMTCT. Furthermore, health economics analysis to examine costs and cost-effectiveness of DTG in late-presenting pregnant women will be conducted

The desired outcome of this project is to establish high quality evidence and operational guidance for use of DTG in late pregnancy. Late-presenting HIV-infected pregnant women are an important, but neglected group of vulnerable individuals in whom a randomised controlled intervention of HIV treatment has never previously been undertaken. This work will be done in relationship with WHO and the Clinton Health Access Initiative to ensure successful delivery of the project objectives.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: An open-label, multi-centre randomised controlled trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Dolutegravir in Pregnant HIV Mothers and Their Neonates
Actual Study Start Date : January 22, 2018
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Dolutegravir

Dolutegravir group (DTG+2 NRTIs) - to make best comparison with standard of care, these NRTIs should be those recommended by national policy.

Participants randomized to the study drug will be commenced on an antiretroviral regimen comprising DTG 50mg once daily in combination with 2 NRTIs

Drug: Dolutegravir
Patients randomized to the study drug will be commenced on an antiretroviral regimen comprising DTG 50mg once daily in combination with 2 NRTIs

Active Comparator: Standard of Care (EFV + 2 NRTI backbone)
Participants randomized to receive standard of care will receive the currently used antiretroviral regimens in keeping with national policy (EFV + 2NRTIs at both study sites).
Drug: Standard of Care (EFV + 2 NRTI backbone)
Patients randomized to receive standard of care will receive the currently used antiretroviral regimens in keeping with national policy.




Primary Outcome Measures :
  1. HIV Viral Load at Delivery [ Time Frame: by delivery ]
    <50 copies/ mL


Secondary Outcome Measures :
  1. Plasma viral load [ Time Frame: By delivery ]
    <1000 copies/ mL

  2. Maternal viral load to 48 weeks [ Time Frame: 48 weeks postpartum ]
    Proportion <50 and <1000 copies/ mL

  3. Maternal viral load to 72 weeks [ Time Frame: 72 weeks postpartum ]
    Proportion <50 and <1000 copies/ mL

  4. Occurrence of MTCT [ Time Frame: 48 weeks postpartum ]
    Proportion of infants with HIV infection

  5. Occurrence of MTCT [ Time Frame: 72 weeks postpartum ]
    Proportion of infants with HIV infection


Other Outcome Measures:
  1. Drug toxicities as defined by DAIDS criteria [ Time Frame: Each study visit up to 72 weeks postpartum ]
    Safety questionnaire

  2. Drug toxicities as defined by DAIDS criteria [ Time Frame: Each study visit up to 72 weeks postpartum ]
    CBC

  3. Drug toxicities as defined by DAIDS criteria [ Time Frame: Each study visit up to 72 weeks postpartum ]
    Serum creatinine (mg/dL)

  4. Drug toxicities as defined by DAIDS criteria [ Time Frame: Each study visit up to 72 weeks postpartum ]
    ALT (U/mL)

  5. Drug toxicities as defined by DAIDS criteria [ Time Frame: Each study visit up to 72 weeks postpartum ]
    Blood urea nitrogen (mg/dL)

  6. Drug toxicities as defined by DAIDS criteria [ Time Frame: Each study visit up to 72 weeks postpartum ]
    Creatine phosphokinase (U/mL)

  7. Safety endpoint: Maternal mental health (Edinburgh Postnatal Depression Scale) [ Time Frame: Enrolment, 4 weeks after ART initiation, every postnatal visit up to 72 weeks postpartum ]
    Edinburgh Postnatal Depression Scale

  8. Safety endpoint: Maternal mental health (Hospital Anxiety and Depression Scale) [ Time Frame: Enrolment, 4 weeks after ART initiation, every postnatal visit up to 72 weeks postpartum ]
    Hospital Anxiety and Depression Scale

  9. Safety of DTG in infant: Birth outcomes (Surface examination for anomalies) [ Time Frame: At birth ]
    Surface examination for anomalies

  10. Safety of DTG in infant: Birth outcomes (Ballard Score for Maturity) [ Time Frame: At birth ]
    Ballard Score for Maturity

  11. Safety of DTG in infant: Birth outcomes (Weight) [ Time Frame: At birth ]
    Weight

  12. Safety of DTG in infant: Birth outcomes (Length) [ Time Frame: At birth ]
    Length

  13. Safety of DTG in infant: Growth and development (Infant gross motor screening tool) [ Time Frame: 24, 48 and 72 weeks postpartum ]
    Infant gross motor screening tool

  14. Safety and tolerability of DTG exposure to infant: Maternal report (Safety questionnaire) [ Time Frame: Delivery and all postnatal follow-up to 72 weeks ]
    Safety questionnaire

  15. Safety of DTG exposure to infant (Blood glucose) [ Time Frame: Delivery and 6 weeks postpartum ]
    Blood glucose

  16. Safety of DTG exposure to infant [ Time Frame: 6 weeks postpartum ]
    ALT (U/mL)

  17. Safety of DTG exposure to infant [ Time Frame: 6 weeks postpartum ]
    Blood urea nitrogen (mg/dL)

  18. Safety of DTG exposure to infant [ Time Frame: 6 weeks postpartum ]
    Serum creatinine (mg/dL)



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

Inclusion Criteria:

  1. Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
  2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  3. Women aged 18 years or older
  4. Pregnant ( ≥28 weeks gestation by best available gestation estimation)
  5. Untreated HIV infection in late pregnancy

Exclusion Criteria:

  1. Received any antiretroviral drugs in previous 12 months
  2. Ever received integrase inhibitors
  3. Previous documented failure of an NNRTI-containing ART regimen, previous EFV-associated toxicity or other history of ARV use that would preclude randomisation based on investigator judgement
  4. Serum haemoglobin <8.0 g/dl
  5. eGFR<50 ml/min*
  6. Elevations in serum levels of alanine aminotransferase (ALT) >5 times the upper limit of normal (ULN) or ALT >3xULN and bilirubin >2xULN (with >35% direct bilirubin).
  7. History or clinical suspicion of unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hyperbilirubinaemia, oesophageal or gastric varices or persistent jaundice).
  8. Severe pre-eclampsia (e.g. HELLP), or other pregnancy related events such as renal or liver abnormalities (e.g. grade 2 or above proteinuria,, total bilirubin, ALT or AST)* at the time of enrolment
  9. Paternal objection for infant participation in DTG arm (where disclosure has taken - applies to Uganda site only
  10. Medical, psychiatric or obstetric condition that might affect participation in the study based on investigator judgement
  11. Receiving any of the following medications (current or within past 2 weeks): anti-epileptic drugs, TB therapy, or other drugs known to significantly interact with either DTG or EFV

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): NCT03249181


Contacts
Contact: Saye H Khoo +441517945560 khoo@liv.ac.uk
Contact: Helen Reynolds +441517945560 her@liverpool.ac.uk

Locations
South Africa
University of Cape Town Recruiting
Cape Town, Western Cape, South Africa
Contact: Landon Myer, MD       landon.myer@uct.ac.za   
Contact: Carmen Delport       carmen.delport@uct.ac.za   
Uganda
Infectious Diseases Institute Recruiting
Kampala, Uganda
Contact: Mohammed Lamorde, MBChB, PhD    +256414307291    mlamorde@idi.co.ug   
Contact: Andrew Kambugu, MBChB, PhD    +256414307227    akambugu@idi.co.ug   
Sub-Investigator: Shadia Nakalema, MBChB         
Sponsors and Collaborators
University of Liverpool
UNITAID
University of Cape Town
Liverpool School of Tropical Medicine
Infectious Diseases Institute, Uganda
Radboud University
Investigators
Study Chair: Saye H Khoo University of Liverpool

Responsible Party: Catriona Waitt, Senior Lecturer in Pharmacology, University of Liverpool
ClinicalTrials.gov Identifier: NCT03249181     History of Changes
Other Study ID Numbers: DolPHIN-2
First Posted: August 15, 2017    Key Record Dates
Last Update Posted: February 16, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Catriona Waitt, University of Liverpool:
MTCT
Antiretroviral
Pregnancy
Africa

Additional relevant MeSH terms:
Dolutegravir
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents