Interactions Between Artemether-lumefantrine and Antiretrovirals in HIV-patients With Uncomplicated Malaria in Tanzania

NCT00885287 | Completed Phase 4 DMC

• 1 other identifier: NIMR/HQ/R.8a/Vol.IX/794
• Study Type: interventional
• Target: 830
• Locations: 1 country
• Sites: 1

Brief Summary

As HIV/AIDS is spreading in malaria-endemic countries, many patients here will need concomitant treatment for both infections. Effective combination treatments are available for both malaria (artemisinin-based combination treatments, ACTs) and HIV/AIDS (antiretroviral combination treatments, ARTs), and these treatments are presently recommended for concomitant use by ministries of health in many endemic countries, including Tanzania. However, theoretically some of these drugs may be involved in harmful interactions with each other, as they share common cytochrome enzymes involved in their metabolism. Such interactions could lead to less effective treatments and/or adverse effects, as a consequence of reduced or increased drug levels, respectively. Only little clinical and pharmacological information is however yet available to guide clinicians and policy-makers on this issue. The main aim of the InterACT study in Tanzania is to conduct a series of detailed observational studies of clinical and paraclinical safety, therapeutic efficacy and pharmacokinetic interactions between the currently nationally recommended first-line treatment for malaria, artemether-lumefantrine, and first-line antiretroviral treatments, primarily nevirapine-based combinations, for HIV/AIDS. The studies will be conducted among patients with uncomplicated malaria, who attend the HIV/AIDS Care and Treatment Clinic and Muheza Designated District Hospital in Muheza, north-eastern Tanzania, which is an area characterized by intense transmission of Plasmodium falciparum malaria and with a prevalence of HIV around 8-10%. The study is expected to inform guidelines for the treatment of malaria in patients with HIV/AIDS in Tanzania, and elsewhere.

Conditions

Malaria, Falciparum; HIV Infections

Keywords

uncomplicated malaria; HIV/AIDS; drug interactions; antimalarial drug efficacy; antiretrovirals; pharmacovigilance; Tanzania

Outcome Measures

Primary Outcomes (1)

• Clinical and parasitological efficacy of artemether-lumefantrine; incidence and severity of treatment-related clinical and paraclinical adverse events; changes in pharmacokinetic profiles of artemether-lumefantrine.

  42 days of post-treatment follow-up

Secondary Outcomes (1)

• Changes in pharmacokinetic profiles of nevirapine-based and other used antiretrovirals;

  42 days of post-treatment follow-up

Study Arms (3)

HIV-positives on ARVs receiving AL for malaria

ACTIVE COMPARATOR

HIV-positive patients on first-line ARVs receiving artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria

Drug: Artemether-lumefantrine (AL)

HIV-positives receiving AL for malaria

ACTIVE COMPARATOR

HIV-positive patients not receiving antiretrovirals but receiving artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria

Drug: Artemether-lumefantrine (AL)

HIV-negatives receiving AL for malaria

ACTIVE COMPARATOR

HIV-negative patients receiving artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria

Drug: Artemether-lumefantrine (AL)

Interventions

Artemether-lumefantrine (AL) DRUG

Standard treatment-dose of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria according to national treatment guidelines

HIV-negatives receiving AL for malaria; HIV-positives on ARVs receiving AL for malaria; HIV-positives receiving AL for malaria

Eligibility Criteria

• Age: 15 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• HIV-positive and HIV-negative patients with confirmed P. falciparum infection in the presence of either measured fever (\> 37.5°C) or a history of fever within the previous 24 hours; for HIV-positive patients also afebrile patients are eligible in the presence of other symptoms of malaria (e.g., coughing, diarrhea, headache, nausea, body weakness, body pain).
• Not being pregnant or lactating.
• Absence of history of clinically significant hypersensitivity reactions to any of the study medicines being evaluated.
• For HIV-positive patients on cART, successful adherence to treatment without prominent adverse events for a period of a minimum of six weeks prior to the date of enrollment will be required.
• Easy access to the health facility (travel time \< 1 hour) and the ability to attend the stipulated follow-up visits.
• Informed consent provided by the patient or by a parent/guardian

You may not qualify if:

• Patients below body weight of 10 kilograms (for under fives).
• Existence of underlying chronic severe illness (e.g., cardiac, renal or hepatic disease).
• No use within the previous four weeks prior to enrollment of any other antimalarial or other drug with antimalarial activity (with the exception of drugs required as part of standard treatment of HIV/AIDS, e.g., sulfamethoxazole and trimethoprim).

Sponsors & Collaborators

• University of Copenhagen: lead
• National Institute for Medical Research, Tanzania: collaborator
• London School of Hygiene and Tropical Medicine: collaborator

Study Sites (1)

Muheza Designated District Hospital

Muheza, Tanga, Tanzania

Location

MeSH Terms

Conditions

Malaria, Falciparum; HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Lasse Vestergaard, MD, PhD

  University of Copenhagen

  PRINCIPAL INVESTIGATOR

• Martha Lemnge, PhD

  National Institute for Medical Research, Tanzania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: April 20, 2009
• First Posted: April 21, 2009
• Study Start: July 1, 2009
• Primary Completion: October 1, 2012
• Study Completion: January 1, 2013
• Last Updated: January 16, 2013

Record last verified: 2013-01

Locations

TA (1)