Vivax MalariaPhase 4VRANCT01178021
Estimating the Risk of Plasmodium Vivax Relapses in Afghanistan
A Phase 4 study testing Chloroquine and Chloroquine/Primaquine in people with Vivax Malaria, run by University of Oxford at 3 sites in Afghanistan.
Trial summary
This is an open label two-arm randomized prospective study of two treatments for P. vivax malaria. Patients meeting study inclusion criteria will be enrolled and allocated either chloroquine alone or chloroquine plus primaquine (0.25mg/kg/day for 14 days). Read more about this study
- Who is it for?
- Ages 6 months and older
- Conditions the study is for
- Vivax Malaria
- What is being tested?
- Chloroquine and Chloroquine/Primaquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 593 participants
- Where
- 3 sitesAfghanistan
- Study dates
- Aug 2009to Feb 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 6 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Adults and children >6 months
- Negative pregnancy test in women at risk of pregnancy
- Microscopic diagnosis of Plasmodium vivax mono-infection (>200/µl asexual forms)
- Axillary temperature ≥37.5°C or oral/rectal temperature ≥38°C or history of fever within the last 24 hours
- Ability to swallow oral medication
- Participant (or parent/guardian if <18 years old) is willing and able to give written informed consent
- Ability (in the investigator's opinion) and willingness of patient or parent/guardian to comply with all study requirements
Who cannot join
- Severe malaria (see WHO definition)
- Patients with microscopic diagnosis of co-infection with Plasmodium falciparum
- Haemoglobin concentration <8g/dl
- Presence of any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study e.g. other acute febrile conditions or chronic disease
- Pregnancy or lactation
- History or phenotypic test compatible with severe G6PD deficiency
- History of hypersensitivity to any of the drugs being tested
Trial locations and contacts
3 sites in 1 country.
Afghanistan3 sites
Provincial Malaria Control Centers (MRC)
Jalalabad
Provincial Malaria Control Centers (MRC)
Kunduz
Provincial Malaria Control Centers (MRC)
Maymana, Faryab Province
About this study
This is an open label two-arm randomized prospective study of two treatments for P. vivax malaria. Patients meeting study inclusion criteria will be enrolled and allocated either chloroquine alone or chloroquine plus primaquine (0.25mg/kg/day for 14 days). Patients will be followed-up for 1 year, with clinical and laboratory examinations at each visit. Patients with recurrent P. vivax infection will be treated with the same medication as initially randomized unless contraindicated. Recurrences in the two arms will be compared to estimate the risk of and mean duration to relapse, classify the relapse pattern as early or late relapse and to estimate the efficacy and safety of the study drugs.
Polymerase Chain Reaction (PCR) analysis will be used as far as possible help to distinguish between relapse and re-infection. Samples for chloroquine pharmacokinetic analysis will be collected on day 7 from each study subject as well as on the day of recurrence if within 8 weeks of chloroquine
Read the detailed description
Globally more than 100 countries are endemic of malaria and about 60% of world population are at risk of getting the infection while around 10% are harboring malaria parasite in their blood stream. Of the four species of plasmodium that infect humans, Plasmodium vivax is responsible for 50% of all malaria cases outside Africa, and is endemic in the Middle East, Asia and Western Pacific, with a lower prevalence in Central and South America a common cause of malaria in many tropical and subtropical regions. Conventional control methods are rather inefficient for preventing transmission of this species of malaria. This is partly due to the persistence of the infectious reservoir, which take the form of latent hypnozoites in the liver, producing recurrent relapses and opportunities for new transmission for several years after initial infection.
Primaquine (PQ) is the only available drug regimen which can eliminate the persisting liver stages (hypnozoites) of P. vivax,but its use for 14 days is ineffective to prevent relapses at 15 mg daily dose (0.25mg/kg) in Southeast Asia and in Brazil, and at a higher dose of 22.5 mg daily in the Southwest Pacific. Due to high relapse rates, a primaquine regimen of 30 mg daily (0.5 mg/kg) for 14 d is now widely recommended for glucose-6-phosphate dehydrogenase (G6PD) normal patients.
P.vivax is the predominant species in Pakistan and eastern Afghanistan. In this area G6PD deficiency is a common trait (7% in Pakistani and 14% in Afghan Pashtoon respectively). However facilities to test for G6PD deficiency are not available and hence routine administration of primaquine is not recommended in national guidelines because of the risk of severe haemolysis in those who cannot be tested.
Several national malaria programmes in Asia have adopted a truncated 5-day course of PQ for vivax malaria to reduce the risk of haemolysis to reasonable levels and to increases compliance rates. Recently this has been documented as being ineffective at reducing relapse rates amongst Afghan refugees in Pakistan while a supervised 14 day course can significantly reduce the frequency of second and third episodes of disease. This is also confirmed by a study in India. Use of the 14 day course is only recommended where the G6PD status of the individual is known, and, currently, where compliance with the full course can be assured. However supervision of patients for 14 day post presentation is seldom feasible in the majority of settings where vivax malaria predominates. Therefore the supposition that patients in a low literacy population will not comply with a 14 day course of treatment in the absence of supervision needs to be confirmed under normal operational conditions. Compliance in taking the drug cannot be monitored by direct observation or by chemical assay of residues in the blood because such interference may, in itself, affect compliance.
- Conditions
- Vivax Malaria
- Being tested
- Chloroquine, Chloroquine/Primaquine
- Keywords
- malaria, vivax, relapse
- Medical subject headings
- Malaria, Vivax, Malaria, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChloroquineDrug
Chloroquine 10 mg/kg on day 0 \& 1 and 5mg/kg on day 2
Chloroquine/PrimaquineDrug
Chloroquine 10 mg/kg on day 0 \& 1 and 5mg/kg on day 2 Primaquine (if given) 0.25mg/kg/day for 14 days
| Study group | Role | What they receive |
|---|---|---|
| Chloroquine | Active comparator | Standard arm Receives: Drug: Chloroquine |
| Chloroquine/Primaquine | Experimental | Chloroquine combined with primaquine Receives: Drug: Chloroquine/Primaquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Secondary vivax attack
Completion of the 1-year (± 1 month) follow-up period without secondary vivax attack
Measured: 1 year
Secondary outcomes (6)
secondary vivax attack
Completion of 6-months (± 1 month) follow-up without secondary vivax attack
Measured: 6 months
G6PD prevalence
G6PD status of patients
Measured: Time of enrollment
Recurrence
Time to first recurrence, median time between episodes of vivax infections and total number of episodes in the follow up period
Measured: 1 year
Days of illness, haematocrit
Overall number of days of illness and haematocrit below 30%
Measured: 1 year
Chloroquine levels
Whole blood chloroquine level at day 7 and any day of recurrence of Plasmodium vivax malaria
Measured: Day 7
Adverse events
Adverse event profiles of chloroquine and primaquine
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2010 (estimated)
- Study startAug 2009
- Primary completionFeb 2014
- Study completionFeb 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Vivax MalariaStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- 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
- 593 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- National Malaria and Leishmaniasis Control Program, Afghanistan, Mahidol University
- Responsible party
- Sponsor
- Investigators
- Ghulam Rahim Awab, MD, Principal investigator, Mahidol Oxford Tropical Medicine Research Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01178021
- Sponsor's protocol ID
- BAKMAL0903
- Acronym
- VRA
- Status last verified
- Jan 2019
- First submitted
- 6 Aug 2010
- Last updated
- 15 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Estimating the Risk of Plasmodium Vivax Relapses in Afghanistan
- ClinicalTrials.gov ID
- NCT01178021
- Acronym / sponsor ID
- VRA / BAKMAL0903
- Conditions
- Vivax Malaria
- Keywords
- malaria, vivax, relapse
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 593 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- National Malaria and Leishmaniasis Control Program, Afghanistan, Mahidol University
- Study start
- Aug 2009 (actual)
- Primary completion
- Feb 2014 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 9 Aug 2010 (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.
This is an open label two-arm randomized prospective study of two treatments for P. vivax malaria. Patients meeting study inclusion criteria will be enrolled and allocated either chloroquine alone or chloroquine plus primaquine (0.25mg/kg/day for 14 days). Patients will be followed-up for 1 year, with clinical and laboratory examinations at each visit. Patients with recurrent P. vivax infection will be treated with the same medication as initially randomized unless contraindicated. Recurrences in the two arms will be compared to estimate the risk of and mean duration to relapse, classify the relapse pattern as early or late relapse and to estimate the efficacy and safety of the study drugs.
Polymerase Chain Reaction (PCR) analysis will be used as far as possible help to distinguish between relapse and re-infection. Samples for chloroquine pharmacokinetic analysis will be collected on day 7 from each study subject as well as on the day of recurrence if within 8 weeks of chloroquine
Detailed description
Globally more than 100 countries are endemic of malaria and about 60% of world population are at risk of getting the infection while around 10% are harboring malaria parasite in their blood stream. Of the four species of plasmodium that infect humans, Plasmodium vivax is responsible for 50% of all malaria cases outside Africa, and is endemic in the Middle East, Asia and Western Pacific, with a lower prevalence in Central and South America a common cause of malaria in many tropical and subtropical regions. Conventional control methods are rather inefficient for preventing transmission of this species of malaria. This is partly due to the persistence of the infectious reservoir, which take the form of latent hypnozoites in the liver, producing recurrent relapses and opportunities for new transmission for several years after initial infection.
Primaquine (PQ) is the only available drug regimen which can eliminate the persisting liver stages (hypnozoites) of P. vivax,but its use for 14 days is ineffective to prevent relapses at 15 mg daily dose (0.25mg/kg) in Southeast Asia and in Brazil, and at a higher dose of 22.5 mg daily in the Southwest Pacific. Due to high relapse rates, a primaquine regimen of 30 mg daily (0.5 mg/kg) for 14 d is now widely recommended for glucose-6-phosphate dehydrogenase (G6PD) normal patients.
P.vivax is the predominant species in Pakistan and eastern Afghanistan. In this area G6PD deficiency is a common trait (7% in Pakistani and 14% in Afghan Pashtoon respectively). However facilities to test for G6PD deficiency are not available and hence routine administration of primaquine is not recommended in national guidelines because of the risk of severe haemolysis in those who cannot be tested.
Several national malaria programmes in Asia have adopted a truncated 5-day course of PQ for vivax malaria to reduce the risk of haemolysis to reasonable levels and to increases compliance rates. Recently this has been documented as being ineffective at reducing relapse rates amongst Afghan refugees in Pakistan while a supervised 14 day course can significantly reduce the frequency of second and third episodes of disease. This is also confirmed by a study in India. Use of the 14 day course is only recommended where the G6PD status of the individual is known, and, currently, where compliance with the full course can be assured. However supervision of patients for 14 day post presentation is seldom feasible in the majority of settings where vivax malaria predominates. Therefore the supposition that patients in a low literacy population will not comply with a 14 day course of treatment in the absence of supervision needs to be confirmed under normal operational conditions. Compliance in taking the drug cannot be monitored by direct observation or by chemical assay of residues in the blood because such interference may, in itself, affect compliance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Chloroquine | Active comparator | Drug: ChloroquineStandard arm |
| Chloroquine/Primaquine | Experimental | Drug: Chloroquine/PrimaquineChloroquine combined with primaquine |
Who may qualify
- Ages
- 6 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Adults and children >6 months
- Negative pregnancy test in women at risk of pregnancy
- Microscopic diagnosis of Plasmodium vivax mono-infection (>200/µl asexual forms)
- Axillary temperature ≥37.5°C or oral/rectal temperature ≥38°C or history of fever within the last 24 hours
- Ability to swallow oral medication
Key exclusion criteria (7 listed)
- Severe malaria (see WHO definition)
- Patients with microscopic diagnosis of co-infection with Plasmodium falciparum
- Haemoglobin concentration <8g/dl
- Presence of any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study e.g. other acute febrile conditions or chronic disease
- Pregnancy or lactation
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 |
|---|---|---|
| ChloroquineChloroquine 10 mg/kg on day 0 \& 1 and 5mg/kg on day 2 | Drug | Chloroquine |
| Chloroquine/PrimaquineChloroquine 10 mg/kg on day 0 \& 1 and 5mg/kg on day 2 Primaquine (if given) 0.25mg/kg/day for 14 days | Drug | Chloroquine/Primaquine |
Primary outcome
Secondary vivax attack
Time frame: 1 year
Completion of the 1-year (± 1 month) follow-up period without secondary vivax attack
6 secondary outcomes
secondary vivax attack
Time frame: 6 months
G6PD prevalence
Time frame: Time of enrollment
Recurrence
Time frame: 1 year
Days of illness, haematocrit
Time frame: 1 year
Chloroquine levels
Time frame: Day 7
Adverse events
Time frame: 1 year
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 15 Jan 2019.
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Induced Blood-Stage Malaria in Healthy Malaria-Naive Adults to Assess the Safety and Infectivity of Plasmodium Vivax Challenge Agent and Evaluate Transmission in Mosquito Feeding Assays
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Safety and Immunogenicity of the Recombinant Malaria Vaccines in Healthy Adults Aged 18-50 Years
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This is a Clinical Study to Assess Whether the Combination of SJ733 and Tafenoquine Will be a Safe and Rapidly Acting Anti-malarial for the Radical Cure of P. Vivax Malaria
Malaria, Malaria Vivax
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.
Ghulam Rahim Awab, MD principal investigator
Mahidol Oxford Tropical Medicine Research Unit
3 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 Chloroquine and Chloroquine/Primaquine in people with Vivax Malaria, run by University of Oxford at 3 sites in Afghanistan.
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 7 inclusion and 7 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 15 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Afghanistan. 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?
Secondary vivax attack (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Jan 2019.