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

This study has been completed.
Sponsor:
Collaborators:
National Institute for Medical Research, Tanzania
London School of Hygiene and Tropical Medicine
Information provided by (Responsible Party):
Lasse Vestergaard, University of Copenhagen
ClinicalTrials.gov Identifier:
NCT00885287
First received: April 20, 2009
Last updated: January 15, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Malaria, Falciparum
HIV Infections
Drug: Artemether-lumefantrine (AL)
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Study of Therapeutic Efficacy, Safety and Pharmacokinetic Interactions Between Artemether-lumefantrine and Nevirapine-based Antiretrovirals in HIV-infected Patients With Uncomplicated Falciparum-malaria in Muheza, Northeastern Tanzania

Resource links provided by NLM:


Further study details as provided by University of Copenhagen:

Primary Outcome Measures:
  • 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. [ Time Frame: 42 days of post-treatment follow-up ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Changes in pharmacokinetic profiles of nevirapine-based and other used antiretrovirals; [ Time Frame: 42 days of post-treatment follow-up ] [ Designated as safety issue: Yes ]

Enrollment: 830
Study Start Date: July 2009
Study Completion Date: January 2013
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: HIV-positives on ARVs receiving AL for malaria
HIV-positive patients on first-line ARVs receiving artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria
Drug: Artemether-lumefantrine (AL)
Standard treatment-dose of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria according to national treatment guidelines
Active Comparator: HIV-positives receiving AL for malaria
HIV-positive patients not receiving antiretrovirals but receiving artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria
Drug: Artemether-lumefantrine (AL)
Standard treatment-dose of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria according to national treatment guidelines
Active Comparator: HIV-negatives receiving AL for malaria
HIV-negative patients receiving artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria
Drug: Artemether-lumefantrine (AL)
Standard treatment-dose of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria according to national treatment guidelines

  Eligibility

Ages Eligible for Study:   15 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00885287

Locations
Tanzania
Muheza Designated District Hospital
Muheza, Tanga Region, Tanzania
Sponsors and Collaborators
University of Copenhagen
National Institute for Medical Research, Tanzania
London School of Hygiene and Tropical Medicine
Investigators
Principal Investigator: Lasse Vestergaard, MD, PhD University of Copenhagen
Principal Investigator: Martha Lemnge, PhD National Institute for Medical Research, Tanzania
  More Information

Additional Information:
No publications provided

Responsible Party: Lasse Vestergaard, Dr, University of Copenhagen
ClinicalTrials.gov Identifier: NCT00885287     History of Changes
Other Study ID Numbers: NIMR/HQ/R.8a/Vol.IX/794
Study First Received: April 20, 2009
Last Updated: January 15, 2013
Health Authority: Tanzania: National Institute for Medical Research

Keywords provided by University of Copenhagen:
uncomplicated malaria
HIV/AIDS
drug interactions
antimalarial drug efficacy
antiretrovirals
pharmacovigilance
Tanzania

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Malaria
Malaria, Falciparum
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Protozoan Infections
Parasitic Diseases
Artemether
Artemisinins
Lumefantrine
Artemether-lumefantrine combination
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Coccidiostats
Schistosomicides
Antiplatyhelmintic Agents
Anthelmintics

ClinicalTrials.gov processed this record on April 16, 2014