Dolutegravir in Pregnant HIV Mothers and Their Neonates

Pregnancy Related Clinical Trial

— DolPHIN-2  

Official title:

Dolutegravir in Pregnant HIV Mothers and Their Neonates

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03249181
• Other study ID #: DolPHIN-2
• Status: Completed
• Phase: Phase 3
• Start date: January 22, 2018
• Est. completion date: September 5, 2023

Study information

• Verified date: November 2023
• Source: University of Liverpool
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 268
• Est. completion date: September 5, 2023
• Est. primary completion date: October 20, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV-1-infection
• Pregnancy Related

Intervention

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
• 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.

Locations

Country	Name	City	State
South Africa	University of Cape Town	Cape Town	Western Cape
Uganda	Infectious Diseases Institute	Kampala

Sponsors (6)

Lead Sponsor	Collaborator
University of Liverpool	Infectious Diseases Institute, Uganda, Liverpool School of Tropical Medicine, Radboud University Medical Center, UNITAID, University of Cape Town

Countries where clinical trial is conducted

South Africa,  Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Drug toxicities as defined by DAIDS criteria	Safety questionnaire	Each study visit up to 72 weeks postpartum
Other	Drug toxicities as defined by DAIDS criteria	CBC	Each study visit up to 72 weeks postpartum
Other	Drug toxicities as defined by DAIDS criteria	Serum creatinine (mg/dL)	Each study visit up to 72 weeks postpartum
Other	Drug toxicities as defined by DAIDS criteria	ALT (U/mL)	Each study visit up to 72 weeks postpartum
Other	Drug toxicities as defined by DAIDS criteria	Blood urea nitrogen (mg/dL)	Each study visit up to 72 weeks postpartum
Other	Drug toxicities as defined by DAIDS criteria	Creatine phosphokinase (U/mL)	Each study visit up to 72 weeks postpartum
Other	Safety endpoint: Maternal mental health (Edinburgh Postnatal Depression Scale)	Edinburgh Postnatal Depression Scale	Enrolment, 4 weeks after ART initiation, every postnatal visit up to 72 weeks postpartum
Other	Safety endpoint: Maternal mental health (Hospital Anxiety and Depression Scale)	Hospital Anxiety and Depression Scale	Enrolment, 4 weeks after ART initiation, every postnatal visit up to 72 weeks postpartum
Other	Safety of DTG in infant: Birth outcomes (Surface examination for anomalies)	Surface examination for anomalies	At birth
Other	Safety of DTG in infant: Birth outcomes (Ballard Score for Maturity)	Ballard Score for Maturity	At birth
Other	Safety of DTG in infant: Birth outcomes (Weight)	Weight	At birth
Other	Safety of DTG in infant: Birth outcomes (Length)	Length	At birth
Other	Safety of DTG in infant: Growth and development (Infant gross motor screening tool)	Infant gross motor screening tool	24, 48 and 72 weeks postpartum
Other	Safety and tolerability of DTG exposure to infant: Maternal report (Safety questionnaire)	Safety questionnaire	Delivery and all postnatal follow-up to 72 weeks
Other	Safety of DTG exposure to infant (Blood glucose)	Blood glucose	Delivery and 6 weeks postpartum
Other	Safety of DTG exposure to infant	ALT (U/mL)	6 weeks postpartum
Other	Safety of DTG exposure to infant	Blood urea nitrogen (mg/dL)	6 weeks postpartum
Other	Safety of DTG exposure to infant	Serum creatinine (mg/dL)	6 weeks postpartum
Primary	HIV Viral Load at Delivery	<50 copies/ mL	by delivery
Secondary	Plasma viral load	<1000 copies/ mL	By delivery
Secondary	Maternal viral load to 48 weeks	Proportion <50 and <1000 copies/ mL	48 weeks postpartum
Secondary	Maternal viral load to 72 weeks	Proportion <50 and <1000 copies/ mL	72 weeks postpartum
Secondary	Occurrence of MTCT	Proportion of infants with HIV infection	48 weeks postpartum
Secondary	Occurrence of MTCT	Proportion of infants with HIV infection	72 weeks postpartum