Plasmodium Vivax InfectionPhase 4NCT01680406
Ethiopia Antimalarial in Vivo Efficacy Study 2012
A Phase 4 study testing Artemether-lumefantrine combination, Primaquine and Chloroquine in people with Plasmodium Vivax Infection, run by Centers for Disease Control and Prevention at 2 sites in Ethiopia.
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%. Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- Plasmodium Vivax Infection
- What is being tested?
- Artemether-lumefantrine combination, Primaquine and Chloroquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 398 participants
- Where
- 2 sitesEthiopia
- Study dates
- Oct 2012to Dec 2014
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
2 sites in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Plasmodium Vivax Infection
- Being tested
- Artemether-lumefantrine combination, Primaquine, Chloroquine
- Keywords
- Plasmodium vivax, malaria, Ethiopia, Sub-Saharan Africa, primaquine, artemether lumefantrine, chloroquine
- Medical subject headings
- Malaria, Vivax, Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Artemether-lumefantrine combinationDrug
PrimaquineDrug
ChloroquineDrug
| Study group | Role | What they receive |
|---|---|---|
| Artemether-lumefantrine | Active comparator | Weight-based dose to be administered as fixed-dose combination twice daily for three days. Receives: Drug: Artemether-lumefantrine combination |
| Artemether-lumefantrine and primaquine | Experimental | 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. Receives: Drug: Artemether-lumefantrine combination; Drug: Primaquine |
| Chloroquine | Active comparator | Chloroquine will be given in a weight-based dose to be administered once daily for three days. Receives: Drug: Chloroquine |
| Chloroquine and primaquine | Experimental | 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. Receives: Drug: Primaquine; Drug: Chloroquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
P. vivax treatment failures following treatment with AL compared to AL+PQ
Measured: day 28 and 42
P. vivax treatment failures following treatment with CQ compared to CQ+PQ
Measured: day 28 and 42
Secondary outcomes (1)
Number of episodes of P. vivax parasitemia over one year following initial effective therapy against P. vivax (i.e. parasite clearance)
Measured: 1 year after day 0 of enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2012 (estimated)
- Study startOct 2012
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Plasmodium Vivax InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 398 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centers for Disease Control and Prevention
- Sponsor type
- US federal agency
- Collaborators
- Ethiopian Health and Nutrition Research Institute, Federal Minstry of Health of Ethiopia, Columbia University, Oromia Regional Health Bureau, Ethiopia, United States Agency for International Development (USAID), Menzies School of Health Research
- Responsible party
- Sponsor
- Investigators
- Jimee Hwang, MD MPH, Principal investigator, Centers for Disease Control and PreventionTesfay Abreha, MSc, MPH, Principal investigator, ICAP-Columbia University, Addis Ababa, EthiopiaDavid Hoos, MD MPH, Principal investigator, ICAP-Columbia University, New York, USA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01680406
- Sponsor's protocol ID
- CDC-CGH-6338
- Status last verified
- Jan 2015
- First submitted
- 30 Aug 2012
- Last updated
- 19 Jan 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Kleinecke M, Sutanto E, Rumaseb A, Hoon KS, Trimarsanto H, Osborne A, Manrique P, Peters T, Hawkes D, Benavente ED, Whitton G, Siegel SV, Pearson RD, Amato R, Rai A, Nhien NTT, Nguyen HC, Assefa A, Degaga TS, Abate DT, Rahim AG, Pasaribu AP, Sutanto I, Alam MS, Pava Z, Lopera-Mesa T, Echeverry D, William T, Anstey NM, Grigg MJ, Day NP, White NJ, Kwiatkowski DP, Taylor AR, Noviyanti R, Neafsey D, Price RN, Auburn S. Microhaplotype deep sequencing assays to capture Plasmodium vivax infection lineages. Nat Commun. 2025 Aug 5;16(1):7192. doi: 10.1038/s41467-025-62357-x.
PubMed 40764298Abreha T, Hwang J, Thriemer K, Tadesse Y, Girma S, Melaku Z, Assef A, Kassa M, Chatfield MD, Landman KZ, Chenet SM, Lucchi NW, Udhayakumar V, Zhou Z, Shi YP, Kachur SP, Jima D, Kebede A, Solomon H, Mekasha A, Alemayehu BH, Malone JL, Dissanayake G, Teka H, Auburn S, von Seidlein L, Price RN. Comparison of artemether-lumefantrine and chloroquine with and without primaquine for the treatment of Plasmodium vivax infection in Ethiopia: A randomized controlled trial. PLoS Med. 2017 May 16;14(5):e1002299. doi: 10.1371/journal.pmed.1002299. eCollection 2017 May.
PubMed 28510573
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01680406
- Acronym / sponsor ID
- CDC-CGH-6338
- Conditions
- Plasmodium Vivax Infection
- Keywords
- Plasmodium vivax, malaria, Ethiopia, Sub-Saharan Africa, primaquine, artemether lumefantrine, chloroquine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 398 participants (actual)
- Lead sponsor
- Centers for Disease Control and PreventionUS federal agency
- Collaborators
- Ethiopian Health and Nutrition Research Institute, Federal Minstry of Health of Ethiopia, Columbia University, Oromia Regional Health Bureau, Ethiopia, United States Agency for International Development (USAID), Menzies School of Health Research
- Study start
- Oct 2012
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 7 Sep 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Artemether-lumefantrine | Active comparator | Drug: Artemether-lumefantrine combinationWeight-based dose to be administered as fixed-dose combination twice daily for three days. |
| Artemether-lumefantrine and primaquine | Experimental | Drug: Artemether-lumefantrine combination, Drug: PrimaquineArtemether-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. |
| Chloroquine | Active comparator | Drug: ChloroquineChloroquine will be given in a weight-based dose to be administered once daily for three days. |
| Chloroquine and primaquine | Experimental | Drug: Primaquine, Drug: ChloroquineChloroquine 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. |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Artemether-lumefantrine combination | Drug | Artemether-lumefantrine, Artemether-lumefantrine and primaquine |
| Primaquine | Drug | Artemether-lumefantrine and primaquine, Chloroquine and primaquine |
| Chloroquine | Drug | Chloroquine, Chloroquine and primaquine |
Primary outcome
P. vivax treatment failures following treatment with AL compared to AL+PQ
Time frame: day 28 and 42
P. vivax treatment failures following treatment with CQ compared to CQ+PQ
Time frame: day 28 and 42
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2017.
- Derived from this study: PubMed 40764298Kleinecke M, Sutanto E, Rumaseb A, Hoon KS, Trimarsanto H, Osborne A, Manrique P, Peters T, Hawkes D, Benavente ED, Whitton G, Siegel SV, Pearson RD, Amato R, Rai A, Nhien NTT, Nguyen HC, Assefa A, Degaga TS, Abate DT, Rahim AG, Pasaribu AP, Sutanto I, Alam MS, Pava Z, Lopera-Mesa T, Echeverry D, William T, Anstey NM, Grigg MJ, Day NP, White NJ, Kwiatkowski DP, Taylor AR, Noviyanti R, Neafsey D, Price RN, Auburn S. Microhaplotype deep sequencing assays to capture Plasmodium vivax infection lineages. Nat Commun. 2025 Aug 5;16(1):7192. doi: 10.1038/s41467-025-62357-x.
- Derived from this study: PubMed 28510573Abreha T, Hwang J, Thriemer K, Tadesse Y, Girma S, Melaku Z, Assef A, Kassa M, Chatfield MD, Landman KZ, Chenet SM, Lucchi NW, Udhayakumar V, Zhou Z, Shi YP, Kachur SP, Jima D, Kebede A, Solomon H, Mekasha A, Alemayehu BH, Malone JL, Dissanayake G, Teka H, Auburn S, von Seidlein L, Price RN. Comparison of artemether-lumefantrine and chloroquine with and without primaquine for the treatment of Plasmodium vivax infection in Ethiopia: A randomized controlled trial. PLoS Med. 2017 May 16;14(5):e1002299. doi: 10.1371/journal.pmed.1002299. eCollection 2017 May.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jimee Hwang, MD MPH principal investigator
Centers for Disease Control and Prevention
Tesfay Abreha, MSc, MPH principal investigator
ICAP-Columbia University, Addis Ababa, Ethiopia
David Hoos, MD MPH principal investigator
ICAP-Columbia University, New York, USA
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Artemether-lumefantrine combination, Primaquine and Chloroquine in people with Plasmodium Vivax Infection, run by Centers for Disease Control and Prevention at 2 sites in Ethiopia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Ethiopia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
P. vivax treatment failures following treatment with AL compared to AL+PQ (time frame: day 28 and 42). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01680406, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2017.