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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03249181
Recruitment Status : Active, not recruiting
First Posted : August 15, 2017
Last Update Posted : September 26, 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

Tracking Information
First Submitted Date  ICMJE July 28, 2017
First Posted Date  ICMJE August 15, 2017
Last Update Posted Date September 26, 2018
Actual Study Start Date  ICMJE January 22, 2018
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 9, 2017)
HIV Viral Load at Delivery [ Time Frame: by delivery ]
<50 copies/ mL
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 9, 2017)
  • Plasma viral load [ Time Frame: By delivery ]
    <1000 copies/ mL
  • Maternal viral load to 48 weeks [ Time Frame: 48 weeks postpartum ]
    Proportion <50 and <1000 copies/ mL
  • Maternal viral load to 72 weeks [ Time Frame: 72 weeks postpartum ]
    Proportion <50 and <1000 copies/ mL
  • Occurrence of MTCT [ Time Frame: 48 weeks postpartum ]
    Proportion of infants with HIV infection
  • Occurrence of MTCT [ Time Frame: 72 weeks postpartum ]
    Proportion of infants with HIV infection
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: August 9, 2017)
  • Drug toxicities as defined by DAIDS criteria [ Time Frame: Each study visit up to 72 weeks postpartum ]
    Safety questionnaire
  • Drug toxicities as defined by DAIDS criteria [ Time Frame: Each study visit up to 72 weeks postpartum ]
    CBC
  • Drug toxicities as defined by DAIDS criteria [ Time Frame: Each study visit up to 72 weeks postpartum ]
    Serum creatinine (mg/dL)
  • Drug toxicities as defined by DAIDS criteria [ Time Frame: Each study visit up to 72 weeks postpartum ]
    ALT (U/mL)
  • Drug toxicities as defined by DAIDS criteria [ Time Frame: Each study visit up to 72 weeks postpartum ]
    Blood urea nitrogen (mg/dL)
  • Drug toxicities as defined by DAIDS criteria [ Time Frame: Each study visit up to 72 weeks postpartum ]
    Creatine phosphokinase (U/mL)
  • 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
  • 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
  • Safety of DTG in infant: Birth outcomes (Surface examination for anomalies) [ Time Frame: At birth ]
    Surface examination for anomalies
  • Safety of DTG in infant: Birth outcomes (Ballard Score for Maturity) [ Time Frame: At birth ]
    Ballard Score for Maturity
  • Safety of DTG in infant: Birth outcomes (Weight) [ Time Frame: At birth ]
    Weight
  • Safety of DTG in infant: Birth outcomes (Length) [ Time Frame: At birth ]
    Length
  • 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
  • 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
  • Safety of DTG exposure to infant (Blood glucose) [ Time Frame: Delivery and 6 weeks postpartum ]
    Blood glucose
  • Safety of DTG exposure to infant [ Time Frame: 6 weeks postpartum ]
    ALT (U/mL)
  • Safety of DTG exposure to infant [ Time Frame: 6 weeks postpartum ]
    Blood urea nitrogen (mg/dL)
  • Safety of DTG exposure to infant [ Time Frame: 6 weeks postpartum ]
    Serum creatinine (mg/dL)
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Dolutegravir in Pregnant HIV Mothers and Their Neonates
Official Title  ICMJE Dolutegravir in Pregnant HIV Mothers and Their Neonates
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)

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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
An open-label, multi-centre randomised controlled trial
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • HIV-1-infection
  • Pregnancy Related
Intervention  ICMJE
  • 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
  • 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.
Study Arms  ICMJE
  • 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

    Intervention: Drug: Dolutegravir
  • 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).
    Intervention: Drug: Standard of Care (EFV + 2 NRTI backbone)
Publications * Kintu K, Malaba TR, Nakibuka J, Papamichael C, Colbers A, Byrne K, Seden K, Hodel EM, Chen T, Twimukye A, Byamugisha J, Reynolds H, Watson V, Burger D, Wang D, Waitt C, Taegtmeyer M, Orrell C, Lamorde M, Myer L, Khoo S; DolPHIN-2 Study Group. Dolutegravir versus efavirenz in women starting HIV therapy in late pregnancy (DolPHIN-2): an open-label, randomised controlled trial. Lancet HIV. 2020 May;7(5):e332-e339. doi: 10.1016/S2352-3018(20)30050-3.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: August 9, 2017)
250
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2021
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE South Africa,   Uganda
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03249181
Other Study ID Numbers  ICMJE DolPHIN-2
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Catriona Waitt, University of Liverpool
Study Sponsor  ICMJE University of Liverpool
Collaborators  ICMJE
  • UNITAID
  • University of Cape Town
  • Liverpool School of Tropical Medicine
  • Infectious Diseases Institute, Uganda
  • Radboud University
Investigators  ICMJE
Study Chair: Saye H Khoo University of Liverpool
PRS Account University of Liverpool
Verification Date September 2018

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