Optimal Dosing of 1st Line Antituberculosis and Antiretroviral Drugs in Children (a Pharmacokinetic Study) (DATiC)
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|ClinicalTrials.gov Identifier: NCT01637558|
Recruitment Status : Completed
First Posted : July 11, 2012
Last Update Posted : October 27, 2017
The aims of this project are to:
- To evaluate the pharmacokinetics of first line antituberculosis drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) when applying the 2010 WHO/IUATLD dosing guidelines across pediatric populations (0-12 years of age, HIV infected and uninfected, and with varied nutritional status) in Cape Town, South Africa and Blantyre, Malawi.
- To evaluate an 8-hourly weight band-based dosing strategy for lopinavir/ritonavir using the commercially available lopinavir/ritonavir (4:1 ratio) in children in South Africa receiving rifampicin-based antituberculosis treatment.
- To evaluate the pharmacokinetics of nevirapine in children in Malawi receiving rifampicin-based antituberculosis treatment.
|Condition or disease||Intervention/treatment||Phase|
|Tuberculosis HIV||Drug: 8 hourly LPV/r during TB treatment Drug: Nevirapine Drug: Lopinavir/Ritonavir||Phase 4|
HIV and tuberculosis are a major public health problem in children. Challenges to treat children with tuberculosis include a lack of knowledge about optimal dosing of first line antituberculosis drugs across ages, nutritional status and HIV infection status, the absence of an appropriate regimen to co-administer rifampin and lopinavir/ritonavir, the key first line drugs for tuberculosis and HIV, and uncertainty about NVP exposure in young children during rifampin-based tuberculosis therapy.
In total, 240 children < 12 years of age with tuberculosis will be enrolled at Red Cross Children's Hospital in Cape Town and Queen Elizabeth Central Hospital, Blantyre. In the second month of antituberculosis treatment, one dose of the drugs in their first-line regimens will be administered according to 2010 WHO/IUATLD guidelines (study drugs) and blood will be sampled for pharmacokinetic analysis over the following 8-10 hours.
Children on antiretroviral treatment (started prior to or during TB treatment) will receive 2 weeks of antiretrovirals (lopinavir/ritonavir or nevirapine) according in the study doses (adjusted 8 hourly doses of lopinavir/ritonavir, or nevirapine doses according to WHO's recommended weight band-based doses) in combination with antituberculosis treatment, prior to pharmacokinetic assessments of both antiretroviral and antituberculosis drugs. Children receiving nevirapine will also undergo pharmacokinetic evaluation 1 month after completion of antituberculosis treatment to evaluate nevirapine concentrations in the absence of antituberculosis drugs. In addition to the 240 children with tuberculosis, 25 HIV infected South African children without tuberculosis will be recruited to evaluate lopinavir concentrations in the absence of antituberculosis drugs.
A population approach will be used to estimate the optimal doses of rifampicin, isoniazid, pyrazinamide and ethambutol in children according to covariates (e.g. age, weight, HIV status, nutritional status) found to have an important influence on the drug concentrations. Similarly population models will be used to describe lopinavir/ritonavir and nevirapine pharmacokinetics in children receiving rifampicin-based antituberculosis treatment, evaluate the dosing approaches and to simulate alternative optimal dosing approaches as indicated.
|Study Type :||Interventional|
|Actual Enrollment :||200 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Optimal Dosing of 1st Line Antituberculosis and Antiretroviral Drugs in Children (a Pharmacokinetic Study)|
|Actual Study Start Date :||November 2012|
|Actual Primary Completion Date :||July 31, 2017|
|Actual Study Completion Date :||July 31, 2017|
No Intervention: Main TB cohort
Children with tuberculosis 0-12 years of age
Experimental: Lopinavir/Ritonavir - Cases
children 3-20 kg with tuberculosis and indication for LPV/r-based ART
Drug: 8 hourly LPV/r during TB treatment
8 hourly LPV/r during TB treatment
Experimental: Lopinavir/Ritonavir - Controls
Children 3-20 kg on LPV/r-based ART; no TB
Experimental: Nevirapine arm
children with TB and indication for nevi rapine-based ART
- Area under the concentration time curve (AUC) for rifampicin, isoniazid, pyrazinamide, ethambutol, lopinavir and nevirapine [ Time Frame: 5 years ]Population PK model-derived AUC's (in mg.h/L)for each of the first line anti-TB drugs, and for the substudies, lopinavir and nevirapine respectively.
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): NCT01637558
|Queen Elizabeth Central Hospital|
|Red Cross Childrens Hospital|
|Cape Town, Western Cape, South Africa, 7700|
|KIDCRU, Tygerberg Hospital, Department of Paediatrics and Child Health, Stellenbosch University, South Africa.|
|Cape Town, Western Cape, South Africa, 7725|
|Desmond Tutu Centre|
|Cape Town, Western Cape, South Africa|
|Principal Investigator:||Helen M McIlleron, PhD||University of Cape Town|
|Principal Investigator:||Heather Zar, PhD||University of Cape Town|