Ethiopia Antimalarial in Vivo Efficacy Study 2012

Plasmodium Vivax Infection Clinical Trial

Official title:

Ethiopia Antimalarial in Vivo Efficacy Study 2012: Evaluating the Efficacy of Artemether-lumefantrine Alone Compared to Artemether-lumefantrine Plus Primaquine and Chloroquine Alone Compared to Chloroquine Plus Primaquine for Plasmodium Vivax Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01680406
• Other study ID #: CDC-CGH-6338
• Status: Completed
• Phase: Phase 4
• First received: August 30, 2012
• Last updated: January 18, 2017
• Start date: October 2012
• Est. completion date: December 2014

Study information

• Verified date: January 2015
• Source: Centers for Disease Control and Prevention
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators hypothesize that the addition of primaquine (PQ) to both artemether-lumefantrine (AL) and chloroquine (CQ) for the treatment of Plasmodium vivax infection will result in decreased chance of relapse by about 60%.

The investigators plan to assess the therapeutic efficacy of AL compared to combined AL + PQ and CQ compared to combined CQ + PQ against P. vivax infection. They also plan to determine the number of recurrent vivax episodes in patients receiving PQ compared to those who don't receive PQ. Patients aged above 1 year with symptomatic malaria presenting to health centers will be enrolled for treatment with AL, AL+PQ, CQ, or CQ+PQ for P. vivax infection.

Phase 1 of the study will monitor the clinical, parasitological, and hematological parameters for P. vivax infection over a 42-day follow-up period, which will be used to evaluate drug efficacy. Phase 2 will continue monthly follow-up of these patients for one year to assess frequency of recurring vivax infections. Results from this research study will be used to assist Ethiopia in assessing their current national malaria drug policies.

Description:

Following the rapid development of significant drug resistance of Plasmodium falciparum (Pf) to chloroquine and then sulfadoxine-pyrimethamine, artemether- lumefantrine (Coartem or AL) was adopted as first line therapy in Ethiopia in 2004. According to the current national malaria diagnosis and treatment guidelines updated in 2012, first-line treatment for uncomplicated P. falciparum infection is AL. First-line treatment for Plasmodium vivax (Pv) is chloroquine (CQ) alone in malarious areas and with primaquine in non-malarious areas at health center and hospital level. WHO recommends treatment of Pv with CQ or an artemisinin-based combination therapy (ACT) in combination with primaquine. For all clinical infection without laboratory confirmation, AL is the first-line treatment since AL is effective against both Pf and Pv. Thus, in Ethiopia, where treatment for malaria without laboratory confirmation occurs frequently, Pv is often treated with AL as the standard of care. Similarly, the recommended drug for mixed infection with Pf and Pv is AL. Now with wide-spread use of AL and CQ and with evidence that malaria laboratory testing is occurring in about half of those suspected with clinical evidence of malaria infection, the investigators propose to conduct an antimalarial efficacy study to monitor the effectiveness of these therapies in Ethiopia and to determine how efficacious these drugs remain for Pv. In addition, with high rates of relapse with P. vivax infection, the efficacy and safety of co-administering primaquine will be assessed. This information will inform future policy changes with respect to appropriate antimalarial strategies.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 398
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year and older

Eligibility

Inclusion Criteria:

• Slide-confirmed infection with P. vivax

• Age > 1 year

• Lives within 20 km of the enrolling health facility

• Weight = 5.0 kg

• Axillary temperature = 37.5º C or history of fever during the previous 48 hours

• Patient or caregiver agrees to all finger pricks and return visits.

Exclusion Criteria:

• General danger signs or symptoms of severe malaria (see Annex II)

• Signs or symptoms of severe malnutrition, defined as weight-for-age = 3 standard deviations below the mean (NCHS/WHO normalized reference values)

• Slide confirmed infection with any other Plasmodium species. besides P. vivax mono-infection

• Acute anemia, defined as Hg < 8 g/dl

• Known hypersensitivity to any of the drugs being evaluated

• Presence of febrile conditions caused by diseases other than malaria

• Serious or chronic medical condition by history (cardiac, renal, hepatic diseases, sickle cell disease, HIV/AIDS)

• Pregnant or breastfeeding women.

• History or hemolysis or severe anemia

• Regular medication, which may interfere with antimalarial pharmacokinetics

Related Conditions & MeSH terms

• Infection
• Malaria
• Plasmodium Vivax Infection

Intervention

Drug:
• Artemether-lumefantrine combination

• Primaquine

• Chloroquine

Locations

Country	Name	City	State
Ethiopia	Bishoftu Malaria Center	Debre Zeit
Ethiopia	Batu Health Center	Zeway

Sponsors (7)

Lead Sponsor	Collaborator
Centers for Disease Control and Prevention	Columbia University, Ethiopian Health and Nutrition Research Institute, Federal Ministry of Health, Ethiopia, Menzies School of Health Research, Oromia Regional Health Bureau, Ethiopia, United States Agency for International Development (USAID)

Country where clinical trial is conducted

Ethiopia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety endpoint	Change in hemoglobin concentration	baseline (day 0) and day 28
Primary	P. vivax treatment failures following treatment with AL compared to AL+PQ		day 28 and 42
Primary	P. vivax treatment failures following treatment with CQ compared to CQ+PQ		day 28 and 42
Secondary	Number of episodes of P. vivax parasitemia over one year following initial effective therapy against P. vivax (i.e. parasite clearance)		1 year after day 0 of enrollment