Malaria Clinical Trial
— OPTIMALOfficial title:
Optimizing Malaria Treatment for HIV-Malaria Co-Infected Individuals by Addressing Drug Interactions Between Artemether-Lumefantrine and Efavirenz; a Randomized Controlled Trial
NCT number | NCT04708496 |
Other study ID # | PK25 |
Secondary ID | |
Status | Recruiting |
Phase | Phase 4 |
First received | |
Last updated | |
Start date | January 18, 2021 |
Est. completion date | March 2024 |
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.
Status | Recruiting |
Enrollment | 888 |
Est. completion date | March 2024 |
Est. primary completion date | January 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. Written informed consent 2. Willing and able to comply with study treatment and procedures 3. Age above 18 years 4. Confirmed HIV positive and receiving efavirenz or dolutegravir based ART for objectives 3 and 4 5. Confirmed Malaria blood film positive without evidence for severe malaria for objectives 3 and 4 6. Confirmed Malaria blood film negative for objectives 1 and 2 Exclusion Criteria: 1. Serum alanine transaminase levels above 3x upper limit of normal 2. Serum creatinine levels above 2x upper limit of normal 3. 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) 4. 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) 5. Likely to be poorly adherent based on clinician's medical judgement 6. Known to be current injection drug user 7. Administration of any additional antimalarial drugs that are not study drugs within 24 hours before study enrollment and during the course of the study. 8. Presence of any non-malarial febrile illness which may interfere with the classification of malaria treatment outcome 9. Movement away from the study area interfering with follow-up assessment 10. Patients with contraindications to taking the study drugs 11. Evidence of QT prolongation on ECG (rate adjusted QT interval>45ms (men (or >470ms for women |
Country | Name | City | State |
---|---|---|---|
Uganda | Infectious Diseases Institute | Kampala | |
Uganda | Tororo District Hospital | Tororo |
Lead Sponsor | Collaborator |
---|---|
Makerere University |
Uganda,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Change Maximum concentration [Cmax] of the antimalarials (Artemether, dihydroartemisinin [DHA], lumefantrin and desbutylumefantrine | Plots of plasma concentration versus time curves will be produced for artemether, dihydroartemisinin, lumefantrine and desbutyl-lumefantrine. Pharmacokinetic parameter Cmax derived directly from the data. The Cmax pharmacokinetic parameter will be presented using descriptive summary statistics including geometric means, geometric mean ratios (GMR) and confidence intervals (CI), or medians and interquartile ranges. The CIs will be determined using logarithms of the individual geometric mean values; the calculated values will be then expressed as linear values. | over 120hours | |
Secondary | Measuring level of Hemoglobin | Anemia is a common with Malaria. The hemoglobin levels will be measured to assess for any reduction and also recovery of the hemoglobin level following treatment. | Hemoglobin will be measured from on follow-up days; 7, 14, 21 and 28. | |
Secondary | Change in Area under the time-concentration curve [AUC] of the antimalarials (Artemether, dihydroartemisinin [DHA], lumefantrin and desbutylumefantrine | Plots of plasma concentration versus time curves will be produced for artemether. AUC over 24 hours (AUC0-24) will be calculated using non-compartmental methods (WinNonlin® Version 6.2, Pharsight). The pharmacokinetic parameter will be presented using descriptive summary statistics including geometric means, geometric mean ratios (GMR) and confidence intervals (CI), or medians and interquartile ranges. The CIs will be determined using logarithms of the individual geometric mean values; the calculated values will be then expressed as linear values. | over 120hours | |
Secondary | Change in Time to maximum concentration [Tmax] of the antimalarials (Artemether, dihydroartemisinin [DHA], lumefantrin and desbutylumefantrine) | Plots of plasma concentration versus time curves will be produced for artemether, dihydroartemisinin, lumefantrine and desbutyl-lumefantrine. Pharmacokinetic parameter time to maximal concentration (Tmax) will be derived directly from the data. The pharmacokinetic parameter will be presented using descriptive summary statistics including geometric means, geometric mean ratios (GMR) and confidence intervals (CI), or medians and interquartile ranges. The CIs will be determined using logarithms of the individual geometric mean values; the calculated values will be then expressed as linear values. | over 120hours | |
Secondary | Change in Clearance [Cl/F] of the antimalarials (Artemether, dihydroartemisinin [DHA], lumefantrin and desbutylumefantrine) | Plots of plasma concentration versus time curves will be produced for artemether, dihydroartemisinin, lumefantrine and desbutyl-lumefantrine. The apparent oral clearance will be calculated using non-compartmental methods (WinNonlin® Version 6.2, Pharsight). This pharmacokinetic parameter will be presented using descriptive summary statistics including geometric means, geometric mean ratios (GMR) and confidence intervals (CI), or medians and interquartile ranges. The CIs will be determined using logarithms of the individual geometric mean values; the calculated values will be then expressed as linear values. | over 120hours | |
Secondary | Change in Trough concentration [Ctrough]) of the antimalarials (Artemether, dihydroartemisinin [DHA], lumefantrin and desbutylumefantrine) | Plots of plasma concentration versus time curves will be produced for artemether, dihydroartemisinin, lumefantrine and desbutyl-lumefantrine. The change in trough concentration will be presented using descriptive summary statistics including geometric means, geometric mean ratios (GMR) and confidence intervals (CI), or medians and interquartile ranges. The CIs will be determined using logarithms of the individual geometric mean values; the calculated values will be then expressed as linear values. | over 120hours | |
Secondary | Prolongation of the QT interval | ECG Monitoring A 12-lead ECG to monitor for QT prolongation will be performed. If any prolongation of the QT interval is observed, the ECGs will be performed at every study visit until normalization. | Over 35days | |
Secondary | Change in the level on the liver enzymes ALT and ALP | Liver Function will be assessed at screening, and on days 7 and 35. Should any derangement in function be observed, the same will be performed at every study visit until normalization. Any participant with deranged liver function will be reported to have either adverse event or serious adverse event depending on the degree of severity and will be further assessed, treated appropriately and followed up till resolution | Over 35days | |
Secondary | Change in creatinine and urea levels | Renal Function will be assessed at screening, and on days 7 and 35. Should any derangement in function be observed, the same will be performed at every study visit until normalization. Any participant with deranged renal function (Creatinine and urea levels) will be reported to have either adverse event or serious adverse event depending on the degree of severity and will be further assessed, treated appropriately and followed up till resolution" Focus will be on monitoring change | Over 35days |
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