Ethiopia Antimalarial in Vivo Efficacy Study 2012

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Centers for Disease Control and Prevention
Sponsor:
Collaborators:
Ethiopia Health and Nutrition Research Institute
Federal Ministry of Health, Ethiopia
Columbia University
Oromia Regional Health Bureau, Ethiopia
United States Agency for International Development (USAID)
Menzies School of Health Research
Information provided by (Responsible Party):
Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:
NCT01680406
First received: August 30, 2012
Last updated: March 6, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Plasmodium Vivax Infection
Drug: Artemether-lumefantrine combination
Drug: Primaquine
Drug: Chloroquine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Centers for Disease Control and Prevention:

Primary Outcome Measures:
  • P. vivax treatment failures in the 4 weeks following treatment with AL compared to AL+PQ [ Time Frame: day 28 ] [ Designated as safety issue: No ]
  • P. vivax treatment failures in the 4 weeks following treatment with CQ compared to CQ+PQ [ Time Frame: day 28 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • P. vivax treatment failures in the 6 weeks following treatment [ Time Frame: Day 42 ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Safety endpoint [ Time Frame: baseline (day 0) and day 28 ] [ Designated as safety issue: Yes ]
    Change in hemoglobin concentration


Estimated Enrollment: 480
Study Start Date: October 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Artemether-lumefantrine
Weight-based dose to be administered as fixed-dose combination twice daily for three days.
Drug: Artemether-lumefantrine combination
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.

Drug: Artemether-lumefantrine combination Drug: Primaquine
Active Comparator: Chloroquine
Chloroquine will be given in a weight-based dose to be administered once daily for three days.
Drug: Chloroquine
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.

Drug: Primaquine Drug: Chloroquine

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.

  Eligibility

Ages Eligible for Study:   1 Year and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01680406

Contacts
Contact: Jimee Hwang, MD, MPH 415-597-4980 gdq1@cdc.gov

Locations
Ethiopia
Bishoftu Malaria Center Recruiting
Debre Zeit, Ethiopia
Contact: Tesfay Abreha, MSc MPH    +251911062800      
Principal Investigator: Tesfay Abreha, MSc MPH         
Batu Health Center Recruiting
Zeway, Ethiopia
Contact: Tesfay Abreha, MSc MPH    +251911062800      
Principal Investigator: Tesfay Abreha, MSc MPH         
Sponsors and Collaborators
Ethiopia Health and Nutrition Research Institute
Federal Ministry of Health, Ethiopia
Columbia University
Oromia Regional Health Bureau, Ethiopia
United States Agency for International Development (USAID)
Menzies School of Health Research
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
  More Information

No publications provided

Responsible Party: Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier: NCT01680406     History of Changes
Other Study ID Numbers: CDC-CGH-6338
Study First Received: August 30, 2012
Last Updated: March 6, 2014
Health Authority: United States: Federal Government

Keywords provided by Centers for Disease Control and Prevention:
Plasmodium vivax
malaria
Ethiopia
Sub-Saharan Africa
primaquine
artemether lumefantrine
chloroquine

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases
Antimalarials
Chloroquine
Chloroquine diphosphate
Primaquine
Artemether
Artemisinins
Lumefantrine
Artemether-lumefantrine combination
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Amebicides
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Filaricides
Antinematodal Agents
Anthelmintics
Central Nervous System Agents
Antifungal Agents

ClinicalTrials.gov processed this record on July 28, 2014