Optimizing Malaria Treatment for HIV-Malaria Co-infected Individuals

NCT04708496 | Unknown Phase 4 DMC

• 1 other identifier: PK25
• Study Type: interventional
• Target: 888
• Locations: 1 country
• Sites: 2

Brief Summary

Optimal is a Randomized clinical trial to optimize treatment of malaria in HIV -malaria co infected patients. It has been demonstrated that, when the antimalarial drug Artemether Lumefantrine is co administered with Efavirenz based ART in HIV-malaria co-infected individuals, sub therapeutic levels of the drug are achieved hence resulting in poor malaria treatment outcomes. The study then hypothesizes that, : HIV-malaria co-infected individuals receiving efavirenz-based ART plus a double-dose or 5-day course of artemether-lumefantrine will achieve higher and adequate artemether-lumefantrine serum concentrations with adequate 42-day treatment outcomes compared to individuals with HIV-malaria co-infection receiving efavirenz-based ART plus a standard-dose of artemether-lumefantrine.

Conditions

HIV Coinfection; Malaria

Outcome Measures

Primary Outcomes (1)

• Measure of malaria treatment outcome adjusted by genotyping and classified as reinfection or recrudescence.

  The Primary outcome measure will be the malaria treatment outcome adjusted by genotyping and classified as reinfection or recrudescence. Treatment outcomes will be classified on the basis of an assessment of the parasitological and clinical outcomes of antimalarial treatment according to the latest WHO guidelines. Thus, all patients will be classified as having early treatment failure, late clinical failure, late parasitological failure or an adequate clinical and parasitological response. Clinical Treatment outcomes will be assessed according to WHO criteria as; early treatment failure and late treatment failure. Parasitological treatment outcomes will be classified as late parasitological failure and adequate clinical and parasitological response.

  Day 42

Secondary Outcomes (9)

• Change Maximum concentration [Cmax] of the antimalarials (Artemether, dihydroartemisinin [DHA], lumefantrin and desbutylumefantrine

  over 120hours

• Measuring level of Hemoglobin

  Hemoglobin will be measured from on follow-up days; 7, 14, 21 and 28.

• Change in Area under the time-concentration curve [AUC] of the antimalarials (Artemether, dihydroartemisinin [DHA], lumefantrin and desbutylumefantrine

  over 120hours

• Change in Time to maximum concentration [Tmax] of the antimalarials (Artemether, dihydroartemisinin [DHA], lumefantrin and desbutylumefantrine)

  over 120hours

• Change in Clearance [Cl/F] of the antimalarials (Artemether, dihydroartemisinin [DHA], lumefantrin and desbutylumefantrine)

  over 120hours

Study Arms (3)

Standard dose of Artemether lumefantrine

EXPERIMENTAL

Dose comparison-concurrent control In this arm, Participants receiving Efavirenz400mg based ART will be randomized to standard dose Artemether Lumefantrine when treating uncomplicated malaria in HIV-malaria co-infected participants

Drug: Artemether-lumefantrine

Double dose Artemether lumefantrine

EXPERIMENTAL

Dose comparison concurrent control In this arm, Participants receiving Efavirenz based ART will be randomized to double dose Artemether Lumefantrine when treating uncomplicated malaria in HIV-malaria co-infected participants

Drug: Artemether-lumefantrine

5 day course of Artemether lumefantrine

EXPERIMENTAL

Dose comparison concurrent control In this arm, Participants receiving Efavirenz based ART will be randomized to 5 day course of Artemether Lumefantrine as opposed to the standard 3day course when treating uncomplicated malaria in HIV-malaria co-infected participants

Drug: Artemether-lumefantrine

Interventions

Artemether-lumefantrine DRUG

A three-arm single blind Randomized Clinical Trial in which HIV-malaria co-infected individuals with uncomplicated malaria receiving efavirenz-based ART will be randomized to one of three arms; a standard dose of artemether-lumefantrine, or a double dose of artemether-lumefantrine, or a 5-day course of artemether-lumefantrine for treatment of uncomplicated malaria. Participants will be followed up for 42 days to determine safety, drug pharmacokinetics and malaria treatment outcomes. The 4th objective focuses on the interaction between Dolutegravir and Artemether Lumefantrine hence this will be a single blind pharmacokinetic trial among HIV-malaria co-infected individuals receiving Dolutegravir based ART and standard dose of artemether-lumefantrine for treatment of uncomplicated malaria.

Also known as: Efavirenz, Dolutegravir

5 day course of Artemether lumefantrine; Double dose Artemether lumefantrine; Standard dose of Artemether lumefantrine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Willing and able to comply with study treatment and procedures
• Age above 18 years
• Confirmed HIV positive and receiving efavirenz or dolutegravir based ART for objectives 3 and 4
• Confirmed Malaria blood film positive without evidence for severe malaria for objectives 3 and 4
• Confirmed Malaria blood film negative for objectives 1 and 2

You may not qualify if:

• Serum alanine transaminase levels above 3x upper limit of normal
• Serum creatinine levels above 2x upper limit of normal
• Use of known inducers/inhibitors of CYP or glucuronyl transferase UGT1A1 within past 2 months (e.g. anticonvulsants, TB medications, HIV agents for prophylaxis, azole antifungals)
• Pregnant women or female subjects who are unwilling to use a suitable contraceptive method for the duration of the study (condom, diaphragm, IUD or contraceptive implant)
• Likely to be poorly adherent based on clinician's medical judgement
• Known to be current injection drug user
• Administration of any additional antimalarial drugs that are not study drugs within 24 hours before study enrollment and during the course of the study.
• Presence of any non-malarial febrile illness which may interfere with the classification of malaria treatment outcome
• Movement away from the study area interfering with follow-up assessment
• Patients with contraindications to taking the study drugs
• Evidence of QT prolongation on ECG (rate adjusted QT interval\>45ms (men (or \>470ms for women

Sponsors & Collaborators

• Makerere University: lead

Study Sites (2)

Infectious Diseases Institute

Kampala, Uganda

COMPLETED

Tororo District Hospital

Tororo, P.O Box 1, Uganda

RECRUITING

MeSH Terms

Conditions

HIV Infections; Malaria

Interventions

Artemether, Lumefantrine Drug Combination; efavirenz; dolutegravir

Condition Hierarchy (Ancestors)

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

• Pauline Byakika-Kibwika, PHD

  IDI

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pauline Byakika-Kibwika, PHD

CONTACT

077262688; pbyakika@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: study physicians and laboratory technicians will be blinded to treatment group assignments.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A three arm single blind randomized trial. Study participants will be randomized to one of the 3 arms. Standard dose, double dose or 5 day course of Artemether-lumefantrine

Study Record Dates

• First Submitted: November 12, 2020
• First Posted: January 14, 2021
• Study Start: January 18, 2021
• Primary Completion: January 1, 2024
• Study Completion: March 1, 2024
• Last Updated: January 6, 2023

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF, CSR

Locations

UG (2)