Ethiopia Antimalarial in Vivo Efficacy Study 2012

January 18, 2017 updated by: Centers for Disease Control and Prevention

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

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.

Study Overview

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

398

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Debre Zeit, Ethiopia
        • Bishoftu Malaria Center
      • Zeway, Ethiopia
        • Batu Health Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Artemether-lumefantrine
Weight-based dose to be administered as fixed-dose combination twice daily for three days.
Experimental: Artemether-lumefantrine and primaquine

Artemether-lumefantrine will be given in a weight-based dose to be administered as fixed-dose combination twice daily for three days.

Primaquine will be given beginning on day 2 of artemether-lumefantrine to patients with a normal G6PD test; dose is weight-based to be administered once daily for 14 days.

Active Comparator: Chloroquine
Chloroquine will be given in a weight-based dose to be administered once daily for three days.
Experimental: Chloroquine and primaquine

Chloroquine will be given in a weight-based dose to be administered once daily for three days.

Primaquine will be given beginning on day 2 of chloroquine to patients with a normal G6PD test; dose is weight-based to be administered once daily for 14 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
P. vivax treatment failures following treatment with AL compared to AL+PQ
Time Frame: day 28 and 42
day 28 and 42
P. vivax treatment failures following treatment with CQ compared to CQ+PQ
Time Frame: day 28 and 42
day 28 and 42

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of episodes of P. vivax parasitemia over one year following initial effective therapy against P. vivax (i.e. parasite clearance)
Time Frame: 1 year after day 0 of enrollment
1 year after day 0 of enrollment

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety endpoint
Time Frame: baseline (day 0) and day 28
Change in hemoglobin concentration
baseline (day 0) and day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Jimee Hwang, MD MPH, Centers for Disease Control and Prevention
  • Principal Investigator: Tesfay Abreha, MSc, MPH, ICAP-Columbia University, Addis Ababa, Ethiopia
  • Principal Investigator: David Hoos, MD MPH, ICAP-Columbia University, New York, USA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2012

Primary Completion (Actual)

December 1, 2014

Study Completion (Actual)

December 1, 2014

Study Registration Dates

First Submitted

August 30, 2012

First Submitted That Met QC Criteria

September 6, 2012

First Posted (Estimate)

September 7, 2012

Study Record Updates

Last Update Posted (Estimate)

January 19, 2017

Last Update Submitted That Met QC Criteria

January 18, 2017

Last Verified

January 1, 2015

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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