HIV InfectionsNCT01828073
Evaluating the Safety and Pharmacokinetics of Raltegravir in Infants
An observational study of HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 19 sites in 5 countries.
Trial summary
The purpose of this study was to determine the washout pharmacokinetics (PK) and safety of in utero/intrapartum exposure to maternal raltegravir (RAL) in infants born to pregnant women with HIV infection who received RAL 400 mg twice daily. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- HIV Infections
- What is being tested?
- Raltegravir
- How many people
- 40 participants
- Where
- 19 sitesin 5 countries
- Study dates
- 19 May 2011to 23 Apr 2018
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Participants were enrolled in two cohorts. Cohort 1 enrolled Mother-Infant (M-I) pairs prior to delivery. Infants expected to be full term (i.e. ≥2000 grams at birth) born to women with HIV-1 infection who received RAL 400 mg twice daily for at least two weeks prior to delivery and continued to receive ARVs during labor, and their mothers, were enrolled to Cohort 1. Cohort 2 enrolled M-I pairs prior to delivery or within 48 hours after delivery. Infants expected to be LBW (i.e. ≤2500 grams at birth) born to women with HIV-1 infection who received at least one dose of RAL 400 mg within 2 to 24 hours prior to delivery, and their mothers, were enrolled to Cohort 2.
Participant study inclusions and exclusion criteria are listed below.
Cohort 1 M-I pairs were enrolled prior to delivery so that only maternal study inclusion and exclusion criteria were assessed at enrollment.
Cohort 1: Maternal Study Inclusion Criteria
- Documentation of HIV-1 infection.
- Viable singleton pregnancy with gestational age of at least 35 weeks based on clinical or other obstetrical measurements with normal fetal anatomy
- Currently receiving RAL 400 mg twice daily for at least 2 weeks prior to enrollment in combination with other ARV agents for clinical care
- Plan to continue taking RAL in combination with other ARV agents through labor prior to delivery
- Willing and intends to deliver at the study-affiliated clinic or hospital
- Willing and able to sign informed consent for participation of herself and her infant. Participant must be of an age to provide legal informed consent as defined by the country in which she resides. If not, informed consent must be signed by a legal guardian.
Cohort 1: Maternal Study Exclusion Criteria
- Receipt of disallowed medications (phenobarbital, phenytoin, rifampin) within 4 weeks prior to enrollment
Cohort 1 Infants were enrolled prior to delivery so there were no infant study inclusion/exclusion criteria. However, only infants who met the following criteria were eligible for PK blood sampling. Infants ineligible for PK sampling remained in the study and were followed-up for safety.
Cohort 1: Infant PK Sampling Inclusion Criteria
- Infant born to women who received at least 2 weeks of RAL prior to delivery and continue to receive RAL during labor prior to delivery in addition to their other ARV drugs
- Infant birth weight of at least 2 kg
- Infant at least 37 weeks gestation at delivery
- Infant not receiving disallowed medications (phenobarbital, phenytoin, rifampin). If these medications are required for the infant's care, the infant will be ineligible for further PK sampling. PK samples will be obtained up to the time of the introduction of the disallowed medication.
Cohort 1: Infant PK Sampling Exclusion Criteria
- Infant has a severe congenital malformation or other medical condition not compatible with life or that would interfere with study participation or interpretation, as judged by the examining clinician
Cohort 2 enrolled M-I pairs at two time points: prior to delivery and within 48 hours after delivery.
- For M-I pairs enrolled prior to delivery, the maternal study eligibility criteria were assessed at enrollment. There were no infant study eligibility criteria. However, only infants who met the PK sampling eligibility criteria had PK blood sampling. Infants ineligible for PK sampling remained in the study and were followed-up for safety.
- For M-I pairs enrolled within 48 hours delivery, the maternal and infant study eligibility criteria were assessed at enrollment. A M-I pair was enrolled only if both the mother and the infant were eligible for the study. For multiple births, only infants who met the study eligibility criteria were enrolled.
Cohort 2: Maternal Study Inclusion Criteria: M-I pairs enrolled prior to delivery
- Documentation of HIV-1 infection.
- Viable singleton or multiple birth pregnancy based on clinical or other obstetrical measurements with infant birth weight anticipated to be less than or equal to 2,500 grams
- RAL is currently used as part of maternal ARV regimen and planned to continue through labor and delivery
- Willing and intends to deliver at the study-affiliated clinic or hospital
- Willing and able to sign informed consent for participation of herself and her infant. Participant must be of an age to provide legal informed consent as defined by the country in which she resides. If not, informed consent must be signed by a legal guardian.
Cohort 2: Maternal Study Exclusion Criteria: M-I pairs enrolled prior to delivery
- Receipt of disallowed medications (phenobarbital, phenytoin, rifampin) within 4 weeks prior to enrollment or intent to be on any of the disallowed medications prior to delivery.
Cohort 2: Infant PK Blood Sampling Eligibility Criteria: M-I pairs enrolled prior to delivery
Infants were enrolled prior to delivery so there were no infant study eligibility criteria. Only infants who met the following criteria were eligible for PK blood sampling:
- Infant born to woman who received at least one dose of RAL within 2 to 24 hours prior to delivery. Dose administered to mother must have been at least 2 hours prior to delivery to allow time for adequate absorption and distribution.
- Infant birth weight less than or equal to 2,500 grams
- Infant not receiving disallowed medications (phenobarbital, phenytoin, rifampin) as described in the protocol. If these medications are required for the infant's care, the infant will be ineligible for further PK sampling. PK data will be obtained up to the time of the introduction of the disallowed medication.
- Infant less than or equal to 48 hours of age
- Infant does not have any severe congenital malformation or other medical condition not compatible with life or that would interfere with study participation or interpretation, as judged by the examining clinician
Cohort 2: Maternal Study Inclusion Criteria: M-I pairs enrolled after delivery
- Documentation of HIV-1 infection.
- Received at least one dose of RAL within 2 to 24 hours prior to delivery
- Willing and able to sign informed consent for participation of herself and her infant. Participant must be of an age to provide legal informed consent as defined by the country in which she resides. If not, informed consent must be signed by a legal guardian.
Cohort 2: Maternal Study Exclusion Criteria: M-I pairs enrolled after delivery
- Receipt of disallowed medications (phenobarbital, phenytoin, rifampin) within 4 weeks prior to delivery
Cohort 2: Infant Study Inclusion Criteria: M-I pairs enrolled after delivery
- Infant birth weight less than or equal to 2,500 grams
- Infant less than or equal to 48 hours of age
Cohort 2: Infant Study Exclusion Criteria: M-I pairs enrolled after delivery
- Received disallowed medications (phenobarbital, phenytoin, rifampin)
- Infant has a severe congenital malformation or other medical condition not compatible with life or that would interfere with study participation or interpretation, as judged by the examining clinician
Trial locations and contacts
19 sites in 5 countries.
19 sites in 5 countries
United States12 sites
Johns Hopkins Univ. Baltimore NICHD CRS
Baltimore, Maryland, 21287
Boston Medical Center Ped. HIV Program NICHD CRS
Boston, Massachusetts, 02118
Univ. of Florida Jacksonville NICHD CRS
Jacksonville, Florida, 32209
University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program
La Jolla, California, 92093-0672
Miller Children's Hosp. Long Beach CA NICHD CRS
Long Beach, California, 90806
Usc La Nichd Crs
Los Angeles, California, 90089
David Geffen School of Medicine at UCLA NICHD CRS
Los Angeles, California, 90095-1752
St. Jude Children's Research Hospital CRS
Memphis, Tennessee, 38105-3678
Univ. of California San Francisco NICHD CRS
San Francisco, California, 94143
Seattle Children's Research Institute CRS
Seattle, Washington, 98101
Bronx-Lebanon Hospital Center NICHD CRS
The Bronx, New York, 10457
Jacobi Med. Ctr. Bronx NICHD CRS
The Bronx, New York, 10461
Brazil4 sites
Hospital Nossa Senhora da Conceicao NICHD CRS
Porto Alegre, Rio Grande do Sul, 91350-200
Hospital Federal dos Servidores do Estado NICHD CRS
Rio de Janeiro, 20221-903
Hosp. Geral De Nova Igaucu Brazil NICHD CRS
Rio de Janeiro, 26030
Univ. of Sao Paulo Brazil NICHD CRS
São Paulo, 14049-900
About this study
Official title: Raltegravir Pharmacokinetics and Safety in Neonates
The purpose of this study was to determine the washout pharmacokinetics (PK) and safety of in utero/intrapartum exposure to maternal raltegravir (RAL) in infants born to pregnant women with HIV infection who received RAL 400 mg twice daily. The study also provided data for the development of an infant RAL starting dosing regimen for IMPAACT P1110 (NCT01780831).
Read the detailed description
Study participants were enrolled in two cohorts.
- Cohort 1 enrolled mother-infant pairs in which the infant was expected to be ≥2000 grams at birth (i.e. full term) at time of enrollment and the mother was living with HIV and received RAL 400 mg twice daily for at least 2 weeks prior to delivery and continued to receive antiretroviral (ARV) drugs during labor.
- Cohort 2 enrolled mother-infant pairs in which the infant was expected to be ≤2500 grams at birth [i.e. low birth weight (LBW)] at time of enrollment and the mother was living with HIV and received at least one dose of RAL 400 mg within 2 to 24 hours prior to delivery.
Cohorts 1 and 2 provided pharmacokinetics and safety data of in utero and intrapartum exposure to maternal RAL in full-term and LBW infants, respectively. Also, the study data were pooled with data from IMPAACT P1066 (NCT00485264) (Cohorts IV and V) and P1026s (NCT00042289) to determine the starting RAL dosing regimen for full-term and LBW infants in IMPAACT P1110 (NCT01780831).
The study initially opened accrual to Cohort 1 under protocol Version 1.0. Upon completion of accrual and follow-up of Cohort 1, the protocol was amended and accrual to and follow-up of Cohort 2 was under protocol Version 2.0.
No study-specific treatment was given to the participants during this study. The women (mothers) received RAL for clinical indications outside of the study. Infants received standard of care ARV therapy for prophylaxis of perinatal transmission of HIV as prescribed by their primary care physicians.
Cohort 1 mother-infant pairs were enrolled prior to delivery. The women were followed-up until discharge from the labor/delivery unit. Infants were followed from birth through 20 weeks after birth. If infant was eligible for PK sampling (see "Eligibility" section), blood samples were collected at 1-5, 8-14, 18-24, and 30-36 hours after birth. Protocol defined infant safety evaluations were at birth, and at 8-14 hours, 30-36 hours, 1 week and 20 weeks after birth.
Cohort 2 mother-infant pairs were enrolled prior to delivery or within 48 hours after delivery. The women were followed-up until discharge from the labor/delivery unit. Infants were followed from birth/entry through 6 weeks after birth. If infant was eligible for PK sampling, blood samples were collected at 1-6, 12-24, 36-48, 72-84, and 108-132 hours and 7-14 days after birth. Protocol defined infant safety evaluations were at entry/birth, and at 36-48 hours, 72-84 hours, 1 week and 6 weeks after birth.
For both cohorts, all infants regardless of whether they were eligible for PK sampling were included in the safety analyses. Infant safety data included adverse birth outcomes, signs/symptoms, diagnoses and chemistry/hematology test results. Protocol required chemistry tests were AST, ALT, serum creatinine, total bilirubin and direct bilirubin. Protocol required hematology tests were CBC with differential and platelet count. Also included in the safety data were additional laboratory events done outside of the study but considered by the site as relevant information.
For both cohorts, maternal blood and cord blood for RAL concentration testing were collected at delivery when specimen collection was possible. The optional genotypic testing (i.e. testing was done only if the mother consented) was limited to infants who were eligible for PK sampling. Information obtained about the effect of UGT1A1 polymorphisms on the PK of RAL was thought to provide a better understanding of the effect of genetics on the metabolism of RAL in neonates.
- Conditions
- HIV Infections
- Being tested
- Raltegravir
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RaltegravirDrug
Also called RAL
No study-specific drugs were given to women or infants during this study. Women received RAL for clinical indications outside of the study.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Full term infants exposed in utero to maternal RAL | Infants, who were expected to be ≥2000 grams at birth (i.e. full-term) at time of enrollment, born to women with HIV-1 infection who received RAL 400 mg twice daily for at least two weeks prior to delivery and continued to receive ARVs during labor. The group also includes the mothers of these infants. Receives: Drug: Raltegravir | |
| Cohort 2: LBW infants exposed in utero to maternal RAL | Infants, who were expected to be ≤2500 grams at birth (i.e. LBW) at time of enrollment, born to women with HIV-1 infection who received at least one dose of RAL 400 mg within 2 to 24 hours prior to delivery. The group also includes the mothers of these infants. Receives: Drug: Raltegravir |
What is being measured
The primary outcome is the main question the study is designed to answer.
PK Parameter: Neonatal RAL Elimination Half-life (T1/2)
Time required for neonatal plasma concentration to decrease by one-half. T1/2 was estimated using the terminal 3 concentration-time points for each infant when available.
Measured: Infant blood specimens were collected at 1-5, 8-14, 18-24, and 30-36 hours after birth for Cohort 1; and at 1-6, 12-24, 36-48, 72-84, and 108-132 hours after birth, and on day 7-14 for Cohort 2.
Ratio of Cord Blood to Maternal Blood RAL Concentrations
Ratio of the neonatal cord blood RAL concentration to the mother's plasma RAL concentration at birth
Measured: Maternal blood samples were scheduled to be collected within 1 hour after delivery and cord blood sample were collected immediately after cord was clamped
Number of Infants Who Met Composite Safety Endpoint (Grade 3/4 Adverse Event, Adverse Birth Outcome, Death)
An infant was said to have met the composite safety endpoint if any of the following was observed:
- adverse events (AEs) of Grade 3 or 4 as defined in DAIDS AE Grading Table
- adverse birth outcomes including stillbirth and low birth weight (LBW), or
- death.
Stillbirth could only be observed on infants enrolled prior to delivery. Cohort 2 enrolled LBW infants and prematurity and growth restriction which were highly linked to LBW were considered as baseline events and not AEs or adverse birth outcome for Cohort 2 infants.
Measured: Assessed at entry through Week 20 for Cohort 1 infants and through Week 6 for Cohort 2 infants.
Infant Total Bilirubin
Total bilirubin measured from infant blood specimens.
Measured: Measured at 8-14 hours (Visit 1), 30-36 hours (Visit 2) and 1-2 weeks (Visit 3) after birth for Cohort 1; and at 36-48 hours (Visit 1), 72-84 hours (Visit 2) and 1 week (Visit 3)after birth for Cohort 2.
Infant Direct Bilirubin
Direct bilirubin measured from infant blood specimens.
Measured: Measured at 8-14 hours (Visit 1), 30-36 hours (Visit 2) and 1-2 weeks (Visit 3) after birth for Cohort 1; and at 36-48 hours (Visit 1), 72-84 hours (Visit 2) and 1 week (Visit 3)after birth for Cohort 2.
Number of Infants Who Received Treatment to Reduce Bilirubin or for Jaundice
Assessment if infant received exchange transfusion, Phototherapy, or other treatment to reduce bilirubin or for jaundice
Measured: Assessed from entry through around week 1 after birth
Secondary outcomes (1)
Neonatal RAL Elimination (T1/2) by UGT1A1 Genotype Group (Normal VS Mutation)
Neonatal RAL elimination was the time required for neonatal plasma concentration to decrease by one-half. Genotyping for polymorphisms of UGT1A1 were performed on infants who were eligible for PK sampling and were consented by their mothers/guardians(i.e. genotyping was optional) . The goal of the genotypic analysis is to determine if certain polymorphisms, particularly those with the UGT1A1*28/*28 genotype have slower RAL elimination than those with the UGT1A1*1/*1 genotype.
Measured: Genotype was assessed close to birth and if this is not possible at 1-2 wks after birth. PK samples were collected at 1-5, 8-14, 18-24 and 30-36 hrs after birth for Cohort 1; 1-6, 12-24, 36-48, 72-84 and 108-132 hrs after birth, and day 7-14 for Cohort 2.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2013 (estimated)
- Study start19 May 2011
- Primary completion23 Apr 2018
- Study completion23 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Diana F. Clarke, PharmD, Study chair, Boston Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01828073
- Sponsor's protocol ID
- P1097
- Other IDs
- 11790, IMPAACT P1097
- Status last verified
- Feb 2020
- First submitted
- 5 Apr 2013
- Last updated
- 8 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Iwamoto M, Wenning LA, Petry AS, Laethem M, De Smet M, Kost JT, Merschman SA, Strohmaier KM, Ramael S, Lasseter KC, Stone JA, Gottesdiener KM, Wagner JA. Safety, tolerability, and pharmacokinetics of raltegravir after single and multiple doses in healthy subjects. Clin Pharmacol Ther. 2008 Feb;83(2):293-9. doi: 10.1038/sj.clpt.6100281. Epub 2007 Aug 22.
PubMed 17713476Wenning LA, Petry AS, Kost JT, Jin B, Breidinger SA, DeLepeleire I, Carlini EJ, Young S, Rushmore T, Wagner F, Lunde NM, Bieberdorf F, Greenberg H, Stone JA, Wagner JA, Iwamoto M. Pharmacokinetics of raltegravir in individuals with UGT1A1 polymorphisms. Clin Pharmacol Ther. 2009 Jun;85(6):623-7. doi: 10.1038/clpt.2009.12. Epub 2009 Mar 11.
PubMed 19279563
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Raltegravir Pharmacokinetics and Safety in Neonates
- ClinicalTrials.gov ID
- NCT01828073
- Acronym / sponsor ID
- P1097
- Conditions
- HIV Infections
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 19 May 2011
- Primary completion
- 23 Apr 2018 (actual)
- Study completion
- 23 Apr 2018 (actual)
- First posted
- 10 Apr 2013 (estimated)
- Results
- Posted 15 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to determine the washout pharmacokinetics (PK) and safety of in utero/intrapartum exposure to maternal raltegravir (RAL) in infants born to pregnant women with HIV infection who received RAL 400 mg twice daily. The study also provided data for the development of an infant RAL starting dosing regimen for IMPAACT P1110 (NCT01780831).
Detailed description
Study participants were enrolled in two cohorts.
- Cohort 1 enrolled mother-infant pairs in which the infant was expected to be ≥2000 grams at birth (i.e. full term) at time of enrollment and the mother was living with HIV and received RAL 400 mg twice daily for at least 2 weeks prior to delivery and continued to receive antiretroviral (ARV) drugs during labor.
- Cohort 2 enrolled mother-infant pairs in which the infant was expected to be ≤2500 grams at birth [i.e. low birth weight (LBW)] at time of enrollment and the mother was living with HIV and received at least one dose of RAL 400 mg within 2 to 24 hours prior to delivery.
Cohorts 1 and 2 provided pharmacokinetics and safety data of in utero and intrapartum exposure to maternal RAL in full-term and LBW infants, respectively. Also, the study data were pooled with data from IMPAACT P1066 (NCT00485264) (Cohorts IV and V) and P1026s (NCT00042289) to determine the starting RAL dosing regimen for full-term and LBW infants in IMPAACT P1110 (NCT01780831).
The study initially opened accrual to Cohort 1 under protocol Version 1.0. Upon completion of accrual and follow-up of Cohort 1, the protocol was amended and accrual to and follow-up of Cohort 2 was under protocol Version 2.0.
No study-specific treatment was given to the participants during this study. The women (mothers) received RAL for clinical indications outside of the study. Infants received standard of care ARV therapy for prophylaxis of perinatal transmission of HIV as prescribed by their primary care physicians.
Cohort 1 mother-infant pairs were enrolled prior to delivery. The women were followed-up until discharge from the labor/delivery unit. Infants were followed from birth through 20 weeks after birth. If infant was eligible for PK sampling (see "Eligibility" section), blood samples were collected at 1-5, 8-14, 18-24, and 30-36 hours after birth. Protocol defined infant safety evaluations were at birth, and at 8-14 hours, 30-36 hours, 1 week and 20 weeks after birth.
Cohort 2 mother-infant pairs were enrolled prior to delivery or within 48 hours after delivery. The women were followed-up until discharge from the labor/delivery unit. Infants were followed from birth/entry through 6 weeks after birth. If infant was eligible for PK sampling, blood samples were collected at 1-6, 12-24, 36-48, 72-84, and 108-132 hours and 7-14 days after birth. Protocol defined infant safety evaluations were at entry/birth, and at 36-48 hours, 72-84 hours, 1 week and 6 weeks after birth.
For both cohorts, all infants regardless of whether they were eligible for PK sampling were included in the safety analyses. Infant safety data included adverse birth outcomes, signs/symptoms, diagnoses and chemistry/hematology test results. Protocol required chemistry tests were AST, ALT, serum creatinine, total bilirubin and direct bilirubin. Protocol required hematology tests were CBC with differential and platelet count. Also included in the safety data were additional laboratory events done outside of the study but considered by the site as relevant information.
For both cohorts, maternal blood and cord blood for RAL concentration testing were collected at delivery when specimen collection was possible. The optional genotypic testing (i.e. testing was done only if the mother consented) was limited to infants who were eligible for PK sampling. Information obtained about the effect of UGT1A1 polymorphisms on the PK of RAL was thought to provide a better understanding of the effect of genetics on the metabolism of RAL in neonates.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Full term infants exposed in utero to maternal RAL | – | Drug: RaltegravirInfants, who were expected to be ≥2000 grams at birth (i.e. full-term) at time of enrollment, born to women with HIV-1 infection who received RAL 400 mg twice daily for at least two weeks prior to delivery and continued to receive ARVs during labor. The group also includes the mothers of these infants. |
| Cohort 2: LBW infants exposed in utero to maternal RAL | – | Drug: RaltegravirInfants, who were expected to be ≤2500 grams at birth (i.e. LBW) at time of enrollment, born to women with HIV-1 infection who received at least one dose of RAL 400 mg within 2 to 24 hours prior to delivery. The group also includes the mothers of these infants. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Participants were enrolled in two cohorts. Cohort 1 enrolled Mother-Infant (M-I) pairs prior to delivery. Infants expected to be full term (i.e. ≥2000 grams at birth) born to women with HIV-1 infection who received RAL 400 mg twice daily for at least two weeks prior to delivery and continued to receive ARVs during labor, and their mothers, were enrolled to Cohort 1. Cohort 2 enrolled M-I pairs prior to delivery or within 48 hours after delivery. Infants expected to be LBW (i.e. ≤2500 grams at birth) born to women with HIV-1 infection who received at least one dose of RAL 400 mg within 2 to 24 hours prior to delivery, and their mothers, were enrolled to Cohort 2.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RaltegravirAlso: RALNo study-specific drugs were given to women or infants during this study. Women received RAL for clinical indications outside of the study. | Drug | Cohort 1: Full term infants exposed in utero to maternal RAL, Cohort 2: LBW infants exposed in utero to maternal RAL |
Primary outcome
PK Parameter: Neonatal RAL Elimination Half-life (T1/2)
Time frame: Infant blood specimens were collected at 1-5, 8-14, 18-24, and 30-36 hours after birth for Cohort 1; and at 1-6, 12-24, 36-48, 72-84, and 108-132 hours after birth, and on day 7-14 for Cohort 2.
Time required for neonatal plasma concentration to decrease by one-half. T1/2 was estimated using the terminal 3 concentration-time points for each infant when available.
Ratio of Cord Blood to Maternal Blood RAL Concentrations
Time frame: Maternal blood samples were scheduled to be collected within 1 hour after delivery and cord blood sample were collected immediately after cord was clamped
Ratio of the neonatal cord blood RAL concentration to the mother's plasma RAL concentration at birth
Number of Infants Who Met Composite Safety Endpoint (Grade 3/4 Adverse Event, Adverse Birth Outcome, Death)
Time frame: Assessed at entry through Week 20 for Cohort 1 infants and through Week 6 for Cohort 2 infants.
An infant was said to have met the composite safety endpoint if any of the following was observed: * adverse events (AEs) of Grade 3 or 4 as defined in DAIDS AE Grading Table * adverse birth outcomes including stillbirth and low birth weight (LBW), or * death. Stillbirth could only be observed on infants enrolled prior to delivery. Cohort 2 enrolled LBW infants and prematurity and growth restriction which were highly linked to LBW were considered as baseline events and not AEs or adverse birth outcome for Cohort 2 infants.
Infant Total Bilirubin
Time frame: Measured at 8-14 hours (Visit 1), 30-36 hours (Visit 2) and 1-2 weeks (Visit 3) after birth for Cohort 1; and at 36-48 hours (Visit 1), 72-84 hours (Visit 2) and 1 week (Visit 3)after birth for Cohort 2.
Total bilirubin measured from infant blood specimens.
Infant Direct Bilirubin
Time frame: Measured at 8-14 hours (Visit 1), 30-36 hours (Visit 2) and 1-2 weeks (Visit 3) after birth for Cohort 1; and at 36-48 hours (Visit 1), 72-84 hours (Visit 2) and 1 week (Visit 3)after birth for Cohort 2.
Direct bilirubin measured from infant blood specimens.
Number of Infants Who Received Treatment to Reduce Bilirubin or for Jaundice
Time frame: Assessed from entry through around week 1 after birth
Assessment if infant received exchange transfusion, Phototherapy, or other treatment to reduce bilirubin or for jaundice
1 secondary outcome
Neonatal RAL Elimination (T1/2) by UGT1A1 Genotype Group (Normal VS Mutation)
Time frame: Genotype was assessed close to birth and if this is not possible at 1-2 wks after birth. PK samples were collected at 1-5, 8-14, 18-24 and 30-36 hrs after birth for Cohort 1; 1-6, 12-24, 36-48, 72-84 and 108-132 hrs after birth, and day 7-14 for Cohort 2.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17713476Iwamoto M, Wenning LA, Petry AS, Laethem M, De Smet M, Kost JT, Merschman SA, Strohmaier KM, Ramael S, Lasseter KC, Stone JA, Gottesdiener KM, Wagner JA. Safety, tolerability, and pharmacokinetics of raltegravir after single and multiple doses in healthy subjects. Clin Pharmacol Ther. 2008 Feb;83(2):293-9. doi: 10.1038/sj.clpt.6100281. Epub 2007 Aug 22.
- Background: PubMed 19279563Wenning LA, Petry AS, Kost JT, Jin B, Breidinger SA, DeLepeleire I, Carlini EJ, Young S, Rushmore T, Wagner F, Lunde NM, Bieberdorf F, Greenberg H, Stone JA, Wagner JA, Iwamoto M. Pharmacokinetics of raltegravir in individuals with UGT1A1 polymorphisms. Clin Pharmacol Ther. 2009 Jun;85(6):623-7. doi: 10.1038/clpt.2009.12. Epub 2009 Mar 11.
- DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, dated December 2004, Clarification August 2009Link provided by the sponsor.
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Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Diana F. Clarke, PharmD study chair
Boston Medical Center
19 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 19 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United States, Brazil, South Africa, Tanzania, Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PK Parameter: Neonatal RAL Elimination Half-life (T1/2) (time frame: Infant blood specimens were collected at 1-5, 8-14, 18-24, and 30-36 hours after birth for Cohort 1; and at 1-6, 12-24, 36-48, 72-84, and 108-132 hours after birth, and on day 7-14 for Cohort 2.). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01828073, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2021.