<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03249181</url>
  </required_header>
  <id_info>
    <org_study_id>DolPHIN-2</org_study_id>
    <nct_id>NCT03249181</nct_id>
  </id_info>
  <brief_title>Dolutegravir in Pregnant HIV Mothers and Their Neonates</brief_title>
  <acronym>DolPHIN-2</acronym>
  <official_title>Dolutegravir in Pregnant HIV Mothers and Their Neonates</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Liverpool</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>UNITAID</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Cape Town</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Liverpool School of Tropical Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Infectious Diseases Institute, Uganda</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Radboud University Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Liverpool</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate dolutegravir (DTG) efficacy in women who present with untreated HIV in late&#xD;
      pregnancy.&#xD;
&#xD;
      An open-label, multi-centre randomised controlled trial of DTG vs efavirenz-based regimens&#xD;
      for women commencing cART in late pregnancy. HIV positive pregnant women presenting with&#xD;
      untreated HIV infection in late (≥28 weeks gestation) pregnancy will be randomised 1:1 to&#xD;
      receive DTG (50mg once daily) + 2 nucleoside reverse transcriptase inhibitors (NRTIs) or EFV&#xD;
      + 2 NRTIs (SoC)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, randomised controlled trial of DTG versus EFV -based regimens for 250&#xD;
      women commencing cART in late pregnancy, randomised 1:1 to DTG vs EFV-based cART. The purpose&#xD;
      of this study is to inform treatment guidelines and for the first time specifically address&#xD;
      the treatment needs of this group of women- hence the trial is powered for superiority over&#xD;
      EFV. The primary endpoints is maternal VL at delivery, with secondary endpoints including&#xD;
      safety and tolerability of DTG in both mother and infant, VL decline in breast milk,&#xD;
      development of drug resistance, pharmacokinetics of DTG in mother-infant pairs,&#xD;
      pharmacogenomics factors relating to efficacy or toxicity of DTG, and MTCT of HIV up to 72&#xD;
      weeks postpartum. Two sites have been selected - Infectious Diseases Institute, Makerere&#xD;
      University, Kampala, Uganda and the University of Cape Town, South Africa - both have a&#xD;
      strong track record of successfully delivering collaborative multidisciplinary research in&#xD;
      PMTCT. Furthermore, health economics analysis to examine costs and cost-effectiveness of DTG&#xD;
      in late-presenting pregnant women will be conducted&#xD;
&#xD;
      The desired outcome of this project is to establish high quality evidence and operational&#xD;
      guidance for use of DTG in late pregnancy. Late-presenting HIV-infected pregnant women are an&#xD;
      important, but neglected group of vulnerable individuals in whom a randomised controlled&#xD;
      intervention of HIV treatment has never previously been undertaken. This work will be done in&#xD;
      relationship with WHO and the Clinton Health Access Initiative to ensure successful delivery&#xD;
      of the project objectives.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 22, 2018</start_date>
  <completion_date type="Anticipated">January 2023</completion_date>
  <primary_completion_date type="Actual">October 20, 2020</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>An open-label, multi-centre randomised controlled trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>HIV Viral Load at Delivery</measure>
    <time_frame>by delivery</time_frame>
    <description>&lt;50 copies/ mL</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Plasma viral load</measure>
    <time_frame>By delivery</time_frame>
    <description>&lt;1000 copies/ mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maternal viral load to 48 weeks</measure>
    <time_frame>48 weeks postpartum</time_frame>
    <description>Proportion &lt;50 and &lt;1000 copies/ mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maternal viral load to 72 weeks</measure>
    <time_frame>72 weeks postpartum</time_frame>
    <description>Proportion &lt;50 and &lt;1000 copies/ mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of MTCT</measure>
    <time_frame>48 weeks postpartum</time_frame>
    <description>Proportion of infants with HIV infection</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of MTCT</measure>
    <time_frame>72 weeks postpartum</time_frame>
    <description>Proportion of infants with HIV infection</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Drug toxicities as defined by DAIDS criteria</measure>
    <time_frame>Each study visit up to 72 weeks postpartum</time_frame>
    <description>Safety questionnaire</description>
  </other_outcome>
  <other_outcome>
    <measure>Drug toxicities as defined by DAIDS criteria</measure>
    <time_frame>Each study visit up to 72 weeks postpartum</time_frame>
    <description>CBC</description>
  </other_outcome>
  <other_outcome>
    <measure>Drug toxicities as defined by DAIDS criteria</measure>
    <time_frame>Each study visit up to 72 weeks postpartum</time_frame>
    <description>Serum creatinine (mg/dL)</description>
  </other_outcome>
  <other_outcome>
    <measure>Drug toxicities as defined by DAIDS criteria</measure>
    <time_frame>Each study visit up to 72 weeks postpartum</time_frame>
    <description>ALT (U/mL)</description>
  </other_outcome>
  <other_outcome>
    <measure>Drug toxicities as defined by DAIDS criteria</measure>
    <time_frame>Each study visit up to 72 weeks postpartum</time_frame>
    <description>Blood urea nitrogen (mg/dL)</description>
  </other_outcome>
  <other_outcome>
    <measure>Drug toxicities as defined by DAIDS criteria</measure>
    <time_frame>Each study visit up to 72 weeks postpartum</time_frame>
    <description>Creatine phosphokinase (U/mL)</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety endpoint: Maternal mental health (Edinburgh Postnatal Depression Scale)</measure>
    <time_frame>Enrolment, 4 weeks after ART initiation, every postnatal visit up to 72 weeks postpartum</time_frame>
    <description>Edinburgh Postnatal Depression Scale</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety endpoint: Maternal mental health (Hospital Anxiety and Depression Scale)</measure>
    <time_frame>Enrolment, 4 weeks after ART initiation, every postnatal visit up to 72 weeks postpartum</time_frame>
    <description>Hospital Anxiety and Depression Scale</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety of DTG in infant: Birth outcomes (Surface examination for anomalies)</measure>
    <time_frame>At birth</time_frame>
    <description>Surface examination for anomalies</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety of DTG in infant: Birth outcomes (Ballard Score for Maturity)</measure>
    <time_frame>At birth</time_frame>
    <description>Ballard Score for Maturity</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety of DTG in infant: Birth outcomes (Weight)</measure>
    <time_frame>At birth</time_frame>
    <description>Weight</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety of DTG in infant: Birth outcomes (Length)</measure>
    <time_frame>At birth</time_frame>
    <description>Length</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety of DTG in infant: Growth and development (Infant gross motor screening tool)</measure>
    <time_frame>24, 48 and 72 weeks postpartum</time_frame>
    <description>Infant gross motor screening tool</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety and tolerability of DTG exposure to infant: Maternal report (Safety questionnaire)</measure>
    <time_frame>Delivery and all postnatal follow-up to 72 weeks</time_frame>
    <description>Safety questionnaire</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety of DTG exposure to infant (Blood glucose)</measure>
    <time_frame>Delivery and 6 weeks postpartum</time_frame>
    <description>Blood glucose</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety of DTG exposure to infant</measure>
    <time_frame>6 weeks postpartum</time_frame>
    <description>ALT (U/mL)</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety of DTG exposure to infant</measure>
    <time_frame>6 weeks postpartum</time_frame>
    <description>Blood urea nitrogen (mg/dL)</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety of DTG exposure to infant</measure>
    <time_frame>6 weeks postpartum</time_frame>
    <description>Serum creatinine (mg/dL)</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">250</enrollment>
  <condition>HIV-1-infection</condition>
  <condition>Pregnancy Related</condition>
  <arm_group>
    <arm_group_label>Dolutegravir</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dolutegravir group (DTG+2 NRTIs) - to make best comparison with standard of care, these NRTIs should be those recommended by national policy.&#xD;
Participants randomized to the study drug will be commenced on an antiretroviral regimen comprising DTG 50mg once daily in combination with 2 NRTIs</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of Care (EFV + 2 NRTI backbone)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dolutegravir</intervention_name>
    <description>Patients randomized to the study drug will be commenced on an antiretroviral regimen comprising DTG 50mg once daily in combination with 2 NRTIs</description>
    <arm_group_label>Dolutegravir</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard of Care (EFV + 2 NRTI backbone)</intervention_name>
    <description>Patients randomized to receive standard of care will receive the currently used antiretroviral regimens in keeping with national policy.</description>
    <arm_group_label>Standard of Care (EFV + 2 NRTI backbone)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Evidence of a personally signed and dated informed consent document indicating that&#xD;
             the participant has been informed of all pertinent aspects of the study.&#xD;
&#xD;
          2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests,&#xD;
             and other study procedures.&#xD;
&#xD;
          3. Women aged 18 years or older&#xD;
&#xD;
          4. Pregnant ( ≥28 weeks gestation by best available gestation estimation)&#xD;
&#xD;
          5. Untreated HIV infection in late pregnancy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Received any antiretroviral drugs in previous 12 months&#xD;
&#xD;
          2. Ever received integrase inhibitors&#xD;
&#xD;
          3. Previous documented failure of an NNRTI-containing ART regimen, previous&#xD;
             EFV-associated toxicity or other history of ARV use that would preclude randomisation&#xD;
             based on investigator judgement&#xD;
&#xD;
          4. Serum haemoglobin &lt;8.0 g/dl&#xD;
&#xD;
          5. eGFR&lt;50 ml/min*&#xD;
&#xD;
          6. Elevations in serum levels of alanine aminotransferase (ALT) &gt;5 times the upper limit&#xD;
             of normal (ULN) or ALT &gt;3xULN and bilirubin &gt;2xULN (with &gt;35% direct bilirubin).&#xD;
&#xD;
          7. History or clinical suspicion of unstable liver disease (as defined by the presence of&#xD;
             ascites, encephalopathy, coagulopathy, hyperbilirubinaemia, oesophageal or gastric&#xD;
             varices or persistent jaundice).&#xD;
&#xD;
          8. Severe pre-eclampsia (e.g. HELLP), or other pregnancy related events such as renal or&#xD;
             liver abnormalities (e.g. grade 2 or above proteinuria,, total bilirubin, ALT or AST)*&#xD;
             at the time of enrolment&#xD;
&#xD;
          9. Paternal objection for infant participation in DTG arm (where disclosure has taken -&#xD;
             applies to Uganda site only&#xD;
&#xD;
         10. Medical, psychiatric or obstetric condition that might affect participation in the&#xD;
             study based on investigator judgement&#xD;
&#xD;
         11. Receiving any of the following medications (current or within past 2 weeks):&#xD;
             anti-epileptic drugs, TB therapy, or other drugs known to significantly interact with&#xD;
             either DTG or EFV&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Saye H Khoo</last_name>
    <role>Study Chair</role>
    <affiliation>University of Liverpool</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Cape Town</name>
      <address>
        <city>Cape Town</city>
        <state>Western Cape</state>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Infectious Diseases Institute</name>
      <address>
        <city>Kampala</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>South Africa</country>
    <country>Uganda</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>July 28, 2017</study_first_submitted>
  <study_first_submitted_qc>August 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>August 8, 2022</last_update_submitted>
  <last_update_submitted_qc>August 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Liverpool</investigator_affiliation>
    <investigator_full_name>Catriona Waitt</investigator_full_name>
    <investigator_title>Senior Lecturer in Pharmacology</investigator_title>
  </responsible_party>
  <keyword>MTCT</keyword>
  <keyword>Antiretroviral</keyword>
  <keyword>Pregnancy</keyword>
  <keyword>Africa</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dolutegravir</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03249181
org study id: DolPHIN-2
nct id: NCT03249181
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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)
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.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: An open-label, multi-centre randomised controlled trial
primary purpose: Treatment
masking: None (Open Label)
measure: HIV Viral Load at Delivery
time frame: by delivery
description: <50 copies/ mL
measure: Plasma viral load
time frame: By delivery
description: <1000 copies/ mL
measure: Maternal viral load to 48 weeks
time frame: 48 weeks postpartum
description: Proportion <50 and <1000 copies/ mL
measure: Maternal viral load to 72 weeks
time frame: 72 weeks postpartum
description: Proportion <50 and <1000 copies/ mL
measure: Occurrence of MTCT
time frame: 48 weeks postpartum
description: Proportion of infants with HIV infection
measure: Occurrence of MTCT
time frame: 72 weeks postpartum
description: Proportion of infants with HIV infection
measure: Drug toxicities as defined by DAIDS criteria
time frame: Each study visit up to 72 weeks postpartum
description: Safety questionnaire
measure: Drug toxicities as defined by DAIDS criteria
time frame: Each study visit up to 72 weeks postpartum
description: CBC
measure: Drug toxicities as defined by DAIDS criteria
time frame: Each study visit up to 72 weeks postpartum
description: Serum creatinine (mg/dL)
measure: Drug toxicities as defined by DAIDS criteria
time frame: Each study visit up to 72 weeks postpartum
description: ALT (U/mL)
measure: Drug toxicities as defined by DAIDS criteria
time frame: Each study visit up to 72 weeks postpartum
description: Blood urea nitrogen (mg/dL)
measure: Drug toxicities as defined by DAIDS criteria
time frame: Each study visit up to 72 weeks postpartum
description: Creatine phosphokinase (U/mL)
measure: 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
description: Edinburgh Postnatal Depression Scale
measure: 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
description: Hospital Anxiety and Depression Scale
measure: Safety of DTG in infant: Birth outcomes (Surface examination for anomalies)
time frame: At birth
description: Surface examination for anomalies
measure: Safety of DTG in infant: Birth outcomes (Ballard Score for Maturity)
time frame: At birth
description: Ballard Score for Maturity
measure: Safety of DTG in infant: Birth outcomes (Weight)
time frame: At birth
description: Weight
measure: Safety of DTG in infant: Birth outcomes (Length)
time frame: At birth
description: Length
measure: Safety of DTG in infant: Growth and development (Infant gross motor screening tool)
time frame: 24, 48 and 72 weeks postpartum
description: Infant gross motor screening tool
measure: Safety and tolerability of DTG exposure to infant: Maternal report (Safety questionnaire)
time frame: Delivery and all postnatal follow-up to 72 weeks
description: Safety questionnaire
measure: Safety of DTG exposure to infant (Blood glucose)
time frame: Delivery and 6 weeks postpartum
description: Blood glucose
measure: Safety of DTG exposure to infant
time frame: 6 weeks postpartum
description: ALT (U/mL)
measure: Safety of DTG exposure to infant
time frame: 6 weeks postpartum
description: Blood urea nitrogen (mg/dL)
measure: Safety of DTG exposure to infant
time frame: 6 weeks postpartum
description: Serum creatinine (mg/dL)
arm group label: Dolutegravir
arm group type: Experimental
description: 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
arm group label: Standard of Care (EFV + 2 NRTI backbone)
arm group type: Active Comparator
description: 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 type: Drug
intervention name: Dolutegravir
description: Patients randomized to the study drug will be commenced on an antiretroviral regimen comprising DTG 50mg once daily in combination with 2 NRTIs
arm group label: Dolutegravir
intervention type: Drug
intervention name: Standard of Care (EFV + 2 NRTI backbone)
description: Patients randomized to receive standard of care will receive the currently used antiretroviral regimens in keeping with national policy.
arm group label: Standard of Care (EFV + 2 NRTI backbone)
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Saye H Khoo
role: Study Chair
affiliation: University of Liverpool
facility: 
facility: 
country: South Africa
country: Uganda
responsible party type: Principal Investigator
investigator affiliation: University of Liverpool
investigator full name: Catriona Waitt
investigator title: Senior Lecturer in Pharmacology
mesh term: Dolutegravir
sharing ipd: No