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IMPAACT P1106: Pharmacokinetic Characteristics of Antiretrovirals and Tuberculosis Medicines in Low Birth Weight Infants

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ClinicalTrials.gov Identifier: NCT02383849
Recruitment Status : Completed
First Posted : March 9, 2015
Last Update Posted : August 6, 2021
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
International Maternal Pediatric Adolescent AIDS Clinical Trials Group

Brief Summary:
P1106 is Phase IV prospective pharmacokinetic (PK) study of low birth weight infants who are receiving or will be receiving as part of clinical care nevirapine (NVP) prophylaxis, tuberculosis (TB) prophylaxis or treatment and/or combination antiretroviral (ARV) treatment containing lopinavir/ritonavir (LPV/r). The study is designed to describe the pharmacokinetics and safety of NVP, INH, RIF, and LPV/r in these infants receiving the drug(s) as part of clinical care.

Condition or disease
Low-Birth-Weight Infant Tuberculosis HIV

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Study Type : Observational
Actual Enrollment : 124 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: IMPAACT P1106: Pharmacokinetic Characteristics of Antiretrovirals and Tuberculosis Medicines in Low Birth Weight Infants
Actual Study Start Date : August 4, 2015
Actual Primary Completion Date : February 14, 2020
Actual Study Completion Date : February 14, 2020

Resource links provided by the National Library of Medicine


Group/Cohort
Arm 1
Breastfeeding infants 7 to 14 days of age with birth weight less than 2500 grams born to HIV-infected mothers not receiving maintenance ARV therapy including NVP; Mother HIV-infected and TB negative; infant receiving NVP prophylaxis but not TB prophylaxis or treatment
Arm 2
Breastfeeding infants 7 to 84 days of age with birth weight less than or equal to 4000 grams born to HIV-infected mothers not receiving maintenance ARV therapy including NVP; Mother HIV-infected with active TB disease; infant receiving NVP prophylaxis plus isoniazid (INH) but not rifampicin (RIF) for TB prophylaxis
Arm 3
Breastfeeding infants 7 to 14 days of age with birth weight less than 2500 grams born to HIV-infected mothers not receiving maintenance ARV therapy including NVP; Mother HIV-infected with active TB disease; infant receiving NVP prophylaxis plus INH plus RIF for TB prophylaxis or treatment
Arm 4
Breast or formula feeding infants 7 to 84 days of age with birth weight less than or equal to 4000 grams born to HIV-uninfected mothers with active TB disease; infant receiving INH alone or INH plus RIF for TB prophylaxis
Arm 5
Breast or formula feeding infants newly diagnosed with HIV infection weighing less than or equal to 4000 grams at birth and are less than or equal to 12 weeks of age. Infants who were enrolled in Arms 1, 2 or 3 and later determined to be HIV infected are then are eligible to enroll in Arm 5 if started on an LPV/r regimen. Infants initiating treatment with LPV/r plus 2 NRTIs, and not receiving RIF (but may be receiving INH)
Arm 6
Breast or formula feeding infants newly diagnosed with HIV infection weighing less than 2500 grams at birth and are less than or equal to 12 weeks of age. Infants who were enrolled in Arms 1, 2 or 3 and later determined to be HIV infected are then are eligible to enroll in Arm 6 if started on an LPV/r regimen. Infants initiating treatment with LPV/r plus 2 NRTIs, and receiving RIF (and may be receiving INH)



Primary Outcome Measures :
  1. Clearance of NVP, INH, RIF, and LPV/r after oral dose [ Time Frame: Week 24 of life ]
    Apparent clearance (CL/F) of NVP, INH, RIF, and LPV/r


Secondary Outcome Measures :
  1. Primary safety endpoints [ Time Frame: Study duration ]
    Number of participants with adverse events of grade 3 or 4 severity, death, or serious adverse clinical events


Biospecimen Retention:   Samples With DNA
Cell pellets from PK sampling once will be combined and stored for a DNA extraction, amplification, and gel electrophoresis. The genotype analysis will be completed one time per study participant. All subjects receiving INH will be genotyped for NAT2. All subjects receiving NVP will be genotyped for CYP 2B6. These genotypes will be used as covariates in the population PK analyses of NVP and INH to determine their impact on CL/F (clearance [apparent]).


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Ages Eligible for Study:   up to 84 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Low birth weight (LBW) infants less than or equal to 2500 grams at birth who are receiving or will be receiving as part of clinical care nevirapine (NVP) prophylaxis, tuberculosis (TB) prophylaxis or treatment and/or combination antiretroviral (ARV) treatment containing lopinavir/ritonavir (LPV/r)
Criteria

Inclusion Criteria:

Inclusion Criteria for Arms 1 and 3 (HIV-exposed infants):

  • Breastfeeding infants born to HIV-infected mothers who are receiving either no ARV therapy or ARV therapy that does not include NVP
  • Age 7 to 14 days
  • Birth weight less than 2500 grams
  • Receiving or will be receiving prophylaxis as prescribed by clinical care provider as follows: NVP (Arm 1), NVP plus INH (Arm 2), NVP plus INH plus RIF (Arm 3)
  • Parent or legal guardian able and willing to provide written informed consent. [Note to sites: modify per locally relevant language].

Inclusion Criteria for Arm 2 (HIV-exposed infants):

  • Breastfeeding infants born to HIV-infected mothers who are receiving either no ARV therapy or ARV therapy that does not include NVP
  • Age 7 to 84 days
  • Birth weight less than or equal to 4000 grams
  • Receiving or will be receiving prophylaxis as prescribed by clinical care provider as follows: NVP (Arm 1), NVP plus INH (Arm 2), NVP plus INH plus RIF (Arm 3)
  • Parent or legal guardian able and willing to provide written informed consent. [Note to sites: modify per locally relevant language].

Inclusion Criteria for Arm 4 (HIV-unexposed but TB exposed infants):

  • Age 7 to 84 days
  • Birth weight less than or equal to 4000 grams
  • Receiving prophylaxis with INH alone or INH plus RIF as prescribed by clinical care provider
  • Not receiving any therapy for HIV prophylaxis or treatment
  • Parent or legal guardian able and willing to provide written informed consent. [Note to sites: modify per locally relevant language].

Inclusion Criteria for Arms 5 and 6 (HIV-infected infants):

  • Documentation of HIV-1 infection defined as positive HIV DNA PCR done as part of clinical care. An HIV RNA confirmatory test must be done at study entry but results may be pending at time of enrollment.
  • Birth weight less than or equal to 4000 grams
  • Age less than or equal to 12 weeks (defined as 84 days)
  • Intention by clinical care provider to prescribe LPV/r plus 2 NRTIs and no RIF (Arm 5) or LPV/r plus 2 NRTIs plus RIF (Arm 6)
  • Parent or legally acceptable representative able and willing to provide written informed consent. [Note to sites: modify per locally relevant language].

Exclusion Criteria:

Any severe congenital malformation or other medical condition incompatible with life or that would interfere with study participation or interpretation, as judged by the examining clinician.


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): NCT02383849


Locations
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South Africa
Soweto IMPAACT CRS (8052)
Johannesburg, Gauteng, South Africa, 1862
Family Clinical Research Unit (FAM-CRU) CRS (8950)
Cape Town, Western Cape Province, South Africa, 7505
Sponsors and Collaborators
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
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Study Chair: Mark Cotton, MD, MBChB, FCPaed, MMED University of Stellenbosch
Study Chair: Mark H Mirochnick, MD Boston Medical Center
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Responsible Party: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT02383849    
Other Study ID Numbers: IMPAACT P1106
11882 ( Other Identifier: DAIDS )
First Posted: March 9, 2015    Key Record Dates
Last Update Posted: August 6, 2021
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data that underlie results in the publication, after deidentification.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: Beginning 3 months following publication and available throughout period of funding of the International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network by NIH.
Access Criteria:
  • With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the IMPAACT Network.
  • For what types of analyses? To achieve aims in the proposal approved by the IMPAACT Network.
  • By what mechanism will data be made available? Researchers may submit a request for access to data using the IMPAACT "Data Request" form at: https://www.impaactnetwork.org/studies/submit-research-proposal. Researchers of approved proposals will need to sign an IMPAACT Data Use Agreement before receiving the data.
Additional relevant MeSH terms:
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Tuberculosis
Body Weight
Birth Weight
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Infections