Antimalarial Pharmacology in Children and Pregnant Women in Uganda

NCT01717885 | Completed

• 2 other identifiers: 10-04798R01HD068174
• Study Type: observational
• Target: 473
• Locations: 1 country
• Sites: 1

Brief Summary

The burden of malaria is greatest in children and pregnant women in sub-Saharan Africa. Malaria is one of the most important infectious diseases in the world. Uganda reports among the highest transmission intensities in the world. Children and pregnant women are the most vulnerable populations. HIV is also reported at high rates for these populations. If malaria and HIV require treatment at the same time, there is a high risk for drug-drug interactions. This study will:

1. 1.Determine if the use of anti-HIV medications including lopinavir/ritonavir (LPV/r), nevirapine (NVP) and efavirenz (EFV) will affect the pharmacokinetic (PK) exposure of antimalarial medications (specifically artemether-lumefantrine, AL) during the treatment for uncomplicated malaria in HIV-infected children and pregnant women, and
2. 2.Evaluate the impact of age and pregnancy on the PK exposure of AL.

Conditions

Malaria; HIV

Keywords

Pharmacokinetics; Antimalarial; HIV; Antiretrovirals; Childhood development; Pregnancy

Outcome Measures

Primary Outcomes (1)

• Primary outcome measurement is the area under the plasma concentration versus time curve for all drug analytes.

  Pharmacokinetic exposure for the antimalarial medication is estimated through sparse or intensive blood sampling around the last dose and for several days following the last dose.

  At time of the last dose of a 6 dose regimen and up to 42 days of F/U

Secondary Outcomes (3)

• Malaria reinfection (recrudescence or new infection)

  From Day 0 to 42 days of F/U when using artemether-lumefantrine for uncomplicated malaria

• Parasite clearance rate

  Days 0 to 42 of follow-up

• AL and ART toxicity

  Days 0 to 42 of follow-up

Study Arms (9)

HIV+children on LPV/r

HIV+ children who are stabilized on a LPV/r based ART regimen

HIV+ children on nevirapine

HIV+ children who are stabilized on an nevirapine based ART regimen

HIV+ children on efavirenz

HIV+ children who are stabilized on an efavirenz based ART regimen

HIV+ pregnant women on LPV/r

HIV+ pregnant women who are stabilized on an LPV/r based ART regimen

HIV+ pregnant women on NVP

HIV+ pregnant women who are stabilized on an nevirapine based ART regimen

HIV+ pregnant women on EFV

HIV+ pregnant women stabilized on an efavirenz based ART regimen

HIV negative children

HIV negative children that will serve as a control for HIV positive children on either a LPV/r, NVP or EFV based ART regimen and will be compared to HIV negative non-pregnant adults

HIV negative adults

HIV negative adults that will serve as a control for comparing results to HIV negative children and HIV negative pregnant women

HIV negative pregnant women

HIV negative pregnant women who will serve as a control for HIV positive pregnant women on either a LPV/r, NVP or EFV based ART regimen and will be compared to HIV negative non-pregnant adults

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

HIV infected and uninfected children and pregnant women residing in Tororo, Uganda and receiving care at local health care facilities including the Tororo District Hospital (TDH), perinatal facilities, HIV clinics and the IDRC research clinic. HIV uninfected children, pregnant women and non-pregnant adults also enrolled through TDH, perinatal facilities or other area clinics. Each participant can enroll at the time they present to one of the clinics with uncomplicated malaria

You may qualify if:

• ALL PARTICIPANTS
• Residency within 60 km of the study clinic
• Agreement to come to clinic for all follow-up clinical and PK evaluations
• Provision of informed consent
• HIV-INFECTED PARTICIPANTS
• Children:
• \) Enrollment in Promote I or meets enrollment criteria and recruited from TDH/TASO or other referral site
• months to 8 years of age
• Weight ≥6 kg
• Confirmed HIV infection (positive rapid HIV test to be confirmed by Western Blot or HIV RNA after enrollment)
• On a stable ART regimen for at least 10 days prior to enrollment
• If co-enrolled from PROMOTE, willingness to undergo intensive PK sampling during a single episode of uncomplicated malaria, and/or population PK/parasite clearance time studies during multiple episodes of uncomplicated malaria.
• If enrolled from TDH, willingness to undergo intensive PK sampling during a single episode of malaria or population PK/parasite clearance time studies during episodes of uncomplicated malaria.
• Pregnant women
• Enrollment in Promote Project 2 or meets enrollment criteria and recruited from TDH/TASO or other referral site

You may not qualify if:

• History of significant comorbidities such as malignancy, active tuberculosis or other WHO stage 4 disease
• Current infection with non-falciparum species
• Receipt of any medications known to affect cytochrome p450 (CYP450) metabolism (except ART) within 14 days of study enrollment (see 4.2.2)
• Hemoglobin \< 7.0 g/dL
• Prior treatment for malaria within 14 days of study enrollment (intensive PK study participants only)
• Signs or evidence of complicated malaria, defined as unarousable coma OR ANY TWO OF THE FOLLOWING SYMPTOMS: Recent febrile convulsions, altered consciousness, lethargy, unable to drink, unable to stand/sit due to weakness, severe anemia (Hb \< 5.0 gm/dL), respiratory distress, jaundice

Sponsors & Collaborators

• University of California, San Francisco: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

IDRC- Tororo Research Clinic and Tororo District Hospital

Tororo, Uganda

Location

Related Publications (4)

• Nyunt MM, Nguyen VK, Kajubi R, Huang L, Ssebuliba J, Kiconco S, Mwima MW, Achan J, Aweeka F, Parikh S, Mwebaza N. Artemether-Lumefantrine Pharmacokinetics and Clinical Response Are Minimally Altered in Pregnant Ugandan Women Treated for Uncomplicated Falciparum Malaria. Antimicrob Agents Chemother. 2015 Dec 14;60(3):1274-82. doi: 10.1128/AAC.01605-15.

  PMID: 26666942 RESULT

• Parikh S, Kajubi R, Huang L, Ssebuliba J, Kiconco S, Gao Q, Li F, Were M, Kakuru A, Achan J, Mwebaza N, Aweeka FT. Antiretroviral Choice for HIV Impacts Antimalarial Exposure and Treatment Outcomes in Ugandan Children. Clin Infect Dis. 2016 Aug 1;63(3):414-22. doi: 10.1093/cid/ciw291. Epub 2016 May 3.

  PMID: 27143666 RESULT

• Kajubi R, Huang L, Were M, Kiconco S, Li F, Marzan F, Gingrich D, Nyunt MM, Ssebuliba J, Mwebaza N, Aweeka FT, Parikh S. Parasite Clearance and Artemether Pharmacokinetics Parameters Over the Course of Artemether-Lumefantrine Treatment for Malaria in Human Immunodeficiency Virus (HIV)-Infected and HIV-Uninfected Ugandan Children. Open Forum Infect Dis. 2016 Dec 15;3(4):ofw217. doi: 10.1093/ofid/ofw217. eCollection 2016 Oct.

  PMID: 28018925 RESULT

• Lehane A, Were M, Wade M, Hamadu M, Cahill M, Kiconco S, Kajubi R, Aweeka F, Mwebaza N, Li F, Parikh S. Comparison on simultaneous caillary and venous parasite density and genotyping results from children and adults with uncomplicated malaria: a prospective observational study in Uganda. BMC Infect Dis. 2019 Jun 26;19(1):559. doi: 10.1186/s12879-019-4174-1.

  PMID: 31242863 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Samples are for drug level measurements,parasite density. RNA samples are for host transcriptional and molecular markers of resistance. Samples are also retained for future use including possible genetic testing for drug metabolism variants

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Francesca T Aweeka, Pharm.D.

  University of California, San Francisco

  STUDY DIRECTOR

• Sunil Parikh, MD MPH

  Yale University

  PRINCIPAL INVESTIGATOR

• Norah Mwebaza, MBChB, MSc

  Makerere University

  PRINCIPAL INVESTIGATOR

• Myaing Nyunt, MD PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2012
• First Posted: October 31, 2012
• Study Start: August 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: September 1, 2016
• Last Updated: October 24, 2024

Record last verified: 2024-10

Locations

UG (1)