Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202012605595028 Date of Approval: 11/12/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Pharmacokinetic Properties of Antiretroviral and Anti-Tuberculosis Drugs during Pregnancy and Postpartum
Official scientific title Pharmacokinetic Properties of Antiretroviral and Anti-Tuberculosis Drugs during Pregnancy and Postpartum
Brief summary describing the background and objectives of the trial Phase IV, prospective, open label, non-randomized PK study that is seeking to describe the pharmacokinetic (PK) properties of antiretroviral (ARV) and anti-tuberculosis (TB) drugs administered during pregnancy and postpartum. The participants are in 5 components depending on the ART they are taking. Primary Objectives Component 1: • To describe the PK parameters during pregnancy of selected ARV drugs administered to WLHIV who are not receiving TB drugs, and to compare these parameters to (a) historical PK data from non-pregnant women and (b) each participant’s own postpartum PK data. Component 2: • To describe the kinetics of (a) placental and breast milk transfer of CAB LA from mother to fetus/infant and (b) infant elimination of CAB LA acquired across the placenta after maternal dosing during pregnancy. Component 3: • To describe the PK parameters during pregnancy and postpartum of selected ARV drugs and first-line TB treatment drugs co-administered to WLHIV. Component 4: • To describe the PK parameters during pregnancy and postpartum of second-line TB treatment drugs administered to WLHIV and HIV-uninfected women. Component 5: • To describe the kinetics of drug transfer of selected ARVs from mother to infant via breast milk. Secondary Objectives All Components: • To describe maternal and infant safety and clinical outcomes. Components 1, 3 and 4: • To compare drug concentrations in plasma from cord blood with concentrations in maternal plasma at delivery for selected ARV and/or TB treatment drugs. • To describe the neonatal elimination of selected ARV and/or TB treatment drugs acquired across the placenta after maternal dosing during pregnancy. Components 3 and 4: • To describe the kinetics of drug transfer of selected ARVs and/or TB treatment drugs from mother to infant via breast milk Component 4: • To describe the PK parameters of selected ARVs when co-administered with selected second-line TB treatment drugs to WLHIV during pregnancy and postpartum.
Type of trial CCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied HIV/AIDS,Tuberculosis
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/02/2021
Actual trial start date
Anticipated date of last follow up 03/12/2021
Actual Last follow-up date
Anticipated target sample size (number of participants) 30
Actual target sample size (number of participants) 325
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
KEMRI SERU 4066 KEMRI
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Non-randomised Central randomisation by phone/fax Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Pharmacokinetics of medications under study 6-9 months Pharmacokinetics will be done for medications that participants will be taking as per local standard of care. 325
Control Group Pharmacokinetics of medications under study 6-9 months Pharmacokinetics of HIV or TB medications that participants will be taking as per local standard of care. 0 Uncontrolled
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Mother is of legal age or otherwise able to provide independent informed consent as determined by site SOPs and consistent with site IRB/EC policies and procedures, and is willing and able to provide written informed consent for her own and her infant’s participation in this study. Prior to study entry, HIV status confirmed as HIV infected At study entry, pregnant and in one of the following two enrollment windows, based on best available obstetrical estimate of gestational age: • Second trimester: gestational age of 20 0/7 to 26 6/7 weeks • Third trimester: gestational age of 30 0/7 to 37 6/7 weeks At study entry, receiving at least two of the following first-line TB treatment drugs under study AND at least one of the following ARV drugs or drug combinations under study, based on maternal report and available medical records: First-line TB treatment drugs: • Isoniazid (INH) 4-6 mg/kg (max 300 mg) q.d. • Rifampin (RIF) 8-12 mg/kg (max 600 mg) q.d. • Rifabutin (RFB) 150-300 mg q.d. • Ethambutol (EMB) 15-20 mg/kg q.d. • Pyrazinamide (PZA) 20-30 mg/kg q.d. • Moxifloxacin (MFX) 400 mg or 800mg q.d. ARVs: Arm 3.1 Dolutegravir (DTG) 50 mg b.i.d. when combined with RIF or 50 mg q.d. if RIF is not part of the TB regimen Arm 3.2 Atazanavir/ritonavir (ATV/r) ≥300/100 mg q.d. or Darunavir/ritonavir (DRV/r) ≥ 600/100 mg b.i.d. Arm 3.3 Lopinavir/ritonavir (LPV/r) 800/200 mg b.i.d. At study entry, has been receiving the drug combination under study at the required dose for at least two weeks based on maternal report and available medical records. At study entry, assessed by study staff as having no identified barriers to completing initial PK sampling within 20 0/7 – 26 6/7 weeks gestation (second trimester) or 30 0/7 to 37 6/7 weeks gestation (third trimester) and within 14 days of enrollment. At study entry, if receiving a generic ARV or TB formulation of the drug or drug combination under study, approval of the formulation. At study entry, mother has received within the past 14 days medicines known to interfere with absorption, metabolism, or clearance of the drug or drug combination under study based on maternal report and available medical records. At study entry, has a clinical or laboratory finding or condition that, in the opinion of the site investigator, is likely to require a change of the ARV or TB drug under study during the period of study follow-up. 4.2.3 Arms 1.3, 1.4 and 1.5 only: At study entry, mother has received TDF-based therapy within the past 6 months. Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Child: 6 Year-12 Year,Infant: 0 Month(s)-12 Month(s),Infant: 13 Month(s)-24 Month(s),Middle Aged: 45 Year(s)-64 Year(s),New born: 0 Day-1 Month,Preschool Child: 2 Year-5 Year 0 Day(s) 50 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 05/11/2020 KENYA MEDICAL RESEARCH INSTITUTE SCIENTIFIC AND ETHICS REVIEW UNIT
Ethics Committee Address
Street address City Postal code Country
Mbagathi Road NAIROBI 00200 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Maternal breast milk/maternal plasma concentration ratio Infant plasma concentration Arms 3.1, 3.2 and 3.3: DTG, ATV, DRV, LPV, INH, RIF, RFB, EMB, PZA, MFX: AUC at 2T, 3T and PP At the end of the trial.
Secondary Outcome Grade 3 or higher maternal adverse events During the trial
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
KENYA MEDICAL RESEARCH INSTITUTE WALTER REED PROJECT CLINICAL RESEARCH CENTER OFF HOSPITAL ROAD KERICHO 20200 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
National Institute of Allergy and Infectious Diseases Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institute of Mental Health 5601 Fishers Lane, Rockville United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor National Institute of Allergy and Infectious Diseases 5601 Fishers Lane Maryland United States of America National Institute of Allergy and Infectious diseases is one of the institutes that form the National Institute of Health of the USA
COLLABORATORS
Name Street address City Postal code Country
Walter Reed Army Institute of Research 503 Robert Grant Avenue Silver Spring Maryland United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator LUCY KOECH lucy.koech@usamru-k.org +254522036100 Off Hospital Road
City Postal code Country Position/Affiliation
Kericho 20200 Kenya Kenya Medical Research Institute Walter Reed Project Clinical Research Center
Role Name Email Phone Street address
Public Enquiries CHARLES KILEL charles.kilel@usamru-k.org +254522036100 Off Hospital Road
City Postal code Country Position/Affiliation
Kericho Kenya Kenya Medical Research Institute Walter Reed Project Clinical Research Center
Role Name Email Phone Street address
Scientific Enquiries LUCY KOECH lucy.koech@usamru-k.org +254522036100 Off Hospital Road
City Postal code Country Position/Affiliation
Kericho 20200 Kenya Kenya Medical Research Institute Walter Reed Project Clinical Research Center
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual participant data will be responsibly shared to support efficient clinical research. Informed Consent Form,Study Protocol Post Trial Title of the clinical trial
URL Results Available Results Summary Result Posting Date First Journal Publication Date
ClinicalTrials.gov No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information