Vivax MalariaPhase 2NCT03529396
Safety and Efficacy of Different Regimens of Primaquine on Vivax Malaria Treatment in G6PD Deficient Patients
A Phase 2 study testing Chloroquine and Primaquine in people with Vivax Malaria and G6PD Deficiency, run by Fundação de Medicina Tropical Dr. Heitor Vieira Dourado at 2 sites in Brazil.
Trial summary
A clinical study to assess the safety and efficacy of alternative regimens of primaquine for radical cure of vivax malaria in glucose 6-phosphate dehydrogenase (G6PD) deficient. G6PD deficient patients with P. Read more about this study
- Who is it for?
- Ages 6 months and older
- Conditions the study is for
- Vivax Malaria, G6PD Deficiency
- What is being tested?
- Chloroquine and Primaquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 106 participants
- Where
- 2 sitesBrazil
- Study dates
- 20 Jul 2018to 6 Jul 2023
- Phase
- Phase 2
- 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
- Uncomplicated vivax malaria monoinfection
- G6PD deficiency ranging from 10%-60% of adjusted mean male activity
- Baseline hemoglobin >9 g/dL
- Willing to comply with study requirements
Who cannot join
- Pregnancy or breastfeeding
- Comorbidities (hepatopathy and/or nephropathy)
- Use of antimalarials in the previous two weeks or current use of potentially hemolytic drugs
- Any condition which would place the subject at undue risk of hemolysis or interfere with the results of the study, as judged by investigator.
Trial locations and contacts
2 sites in 1 country.
Brazil2 sites
Fundação de Medicina Tropical Doutor Heitor Vieira Dourado
Manaus, Amazonas, 69040-000
Centro de Pesquisa em Medicina Tropical (Cepem)
Porto Velho, Rondônia
About this study
Official title: Safety and Efficacy of Different Regimens of Primaquine on Vivax Malaria Treatment in Glucose 6-phosphate Dehydrogenase Deficient Patients
A clinical study to assess the safety and efficacy of alternative regimens of primaquine for radical cure of vivax malaria in glucose 6-phosphate dehydrogenase (G6PD) deficient. G6PD deficient patients with P. vivax monoinfection will be treated with either weekly or delayed one-week course of primaquine, and the currently recommended by national guideline, 12-week chloroquine regimen to compare treatment safety among groups. All groups will be actively monitored for hemolysis during treatment and will have six-month follow-up period to assess treatment efficacy.
Read the detailed description
This is an open-label, randomized, phase II, clinical trial of safety and efficacy. Patients will be screened for eligibility and treated at the Fundação de Medicina Tropical Dr Heitor Vieira Dourado in Manaus and the Centro de Pesquisa em Medicina Tropical (Cepem) in Porto Velho, Brazil. A total of 104 vivax malaria patients will be recruited into the study, 52 G6PD deficient (Arm 1) and 52 G6PD normal (Arm 2). Patients with spectrophotometrically-confirmed G6PD deficiency (10-60% of adjusted mean male activity) will be divided into three subgroups of 10 patient each. All arms will receive standard 3-day chloroquine course. Additionally, Arm 1a will receive a delayed course of primaquine for 7 days, starting only at the fifth-day post-chloroquine initiation [ARM HALTED DUE TO SAFETY CONCERNS]. Arm 1b will receive weekly primaquine, once a week, for 8 weeks. Arm 1c will receive prophylactic 12-week course of chloroquine, as recommended by national guidelines for such patients (control group in terms of safety). Arm 2, the control group of efficacy, will receive standard regimen, comprised of 3-day chloroquine plus concomitant 7-day primaquine. All patients will receive directly observed therapy (DOT) and will be closely monitored for clinical parameters and laboratory markers of hemolysis including hemoglobin, methemoglobin, lactate dehydrogenase, haptoglobin, reticulocytes, indirect bilirubin, aspartate aminotransferase, and urinalysis. All groups will be followed for 6 months after treatment to assess relapse rate. Primary endpoint is the tolerability of the regimens defined by hemoglobin fall. Secondary endpoints include treatment failure (relapse during follow-up), frequency of adverse effects, and rate of hemoglobin fall during treatment.
- Conditions
- Vivax Malaria, G6PD Deficiency
- Being tested
- Chloroquine, Primaquine
- Keywords
- G6PD deficiency, Acute hemolytic anemia, Vivax malaria, Primaquine, Weekly primaquine, Chloroquine, Weekly chloroquine, Brazilian Amazon, Oxidative stress
- Medical subject headings
- Malaria, Vivax, Glucosephosphate Dehydrogenase Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChloroquineDrug
Standard chloroquine (three days)
PrimaquineDrug
Daily Primaquine (0.5 mg of base/kg/day for seven days) starting only at the fifth day post chloroquine initiation.
PrimaquineDrug
Weekly primaquine (0.75 mg of base/kg/week for eight weeks) starting with first dose of chloroquine.
ChloroquineDrug
Weekly, once a week chloroquine (5 mg of base/kg/week for twelve weeks)
PrimaquineDrug
Standard primaquine (0.5mg of base/kg/day for seven days) concomitant with chloroquine.
| Study group | Role | What they receive |
|---|---|---|
| 1a: Chloroquine + 5th-day Primaquine | Experimental | [ARM HALTED PREMATURELY DUE TO SAFETY CONCERNS] Receives: Drug: Chloroquine; Drug: Primaquine |
| 1b: Chloroquine + 8-week Primaquine | Experimental | 26 G6PD deficient patients. Directly observed therapy. Receives: Drug: Chloroquine; Drug: Primaquine |
| 1c: Chloroquine + 12-week Chloroquine | Active comparator | 26 G6PD deficient patients. Control group in terms of safety. Directly observed therapy. Receives: Drug: Chloroquine |
| 2: Standard chloroquine + primaquine | Active comparator | 52 G6PD normal patients. Control group in terms of efficacy. Directly observed therapy. Receives: Drug: Chloroquine; Drug: Primaquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Absolute or relative change in hemoglobin < 3g/dL or 30% from baseline
Hemoglobin reduction from baseline after exposure to primaquine for P. vivax treatment
Measured: From date of randomization until the date of last dose, assessed up to 12 weeks.
Secondary outcomes (3)
Regimen efficacy
Relapse rate over follow-up period after treatment
Measured: 6 months post treatment
Adverse effects
Presence of adverse reactions as a result of intervention, measured by clinical and laboratory tests
Measured: From date of randomization until the date of first documented event, assessed up to 12 weeks.
Change in hemoglobin values over treatment
Absolute variation of hemoglobin levels before and during intervention.
Measured: through study completion: before intervention and up to 12 weeks during intervention.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2018
- Study start20 Jul 2018
- Primary completion20 Dec 2022
- Study completion6 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Vivax MalariaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
- Sponsor type
- University, hospital or other
- Collaborators
- Oswaldo Cruz Foundation, Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Responsible party
- Principal investigator, Wuelton Marcelo Monteiro, PhD, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
- Investigators
- Marcus VG Lacerda, MD, PhD, Principal investigator, Fiocruz/ILMD and Fundacao de Medicina Tropical Dr Heitor Vieira Dourado
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03529396
- Sponsor's protocol ID
- CAAE: 70177317.1.0000.0005
- Status last verified
- Feb 2025
- First submitted
- 25 Apr 2018
- Last updated
- 20 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Barbosa L, Brito-Sousa J, Nascimento C, Pacheco A, Alexandre M, Alencar A, Melo M, Omena A, Souza I, Silva E, Queiroz M, Siqueira V, Rabelo C, Baia-da-Silva D, Silva D, Rocha Y, Barbosa A, Castro R, Almeida A, Brito M, Lopes A, Balieiro A, Costa M, Amaral T, Valle C, Vieira A, Gonzaga J, Pereira D, Alecrim M, Monteiro W, Lacerda M, Melo G. Safety and Efficacy of 3 Alternative Regimens Against Relapsing Plasmodium vivax Malaria in Glucose 6-Phosphate Dehydrogenase-Deficient Patients in the Brazilian Amazon (ALTPRIM). Clin Infect Dis. 2025 Dec 24;81(5):e294-e301. doi: 10.1093/cid/ciaf007.
PubMed 39785834
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Different Regimens of Primaquine on Vivax Malaria Treatment in Glucose 6-phosphate Dehydrogenase Deficient Patients
- ClinicalTrials.gov ID
- NCT03529396
- Acronym / sponsor ID
- CAAE: 70177317.1.0000.0005
- Conditions
- Vivax Malaria, G6PD Deficiency
- Keywords
- G6PD deficiency, Acute hemolytic anemia, Vivax malaria, Primaquine, Weekly primaquine, Chloroquine, Weekly chloroquine, Brazilian Amazon
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- Fundação de Medicina Tropical Dr. Heitor Vieira DouradoUniversity, hospital or other
- Collaborators
- Oswaldo Cruz Foundation, Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Study start
- 20 Jul 2018 (actual)
- Primary completion
- 20 Dec 2022 (actual)
- Study completion
- 6 Jul 2023 (actual)
- First posted
- 18 May 2018 (actual)
- 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.
A clinical study to assess the safety and efficacy of alternative regimens of primaquine for radical cure of vivax malaria in glucose 6-phosphate dehydrogenase (G6PD) deficient. G6PD deficient patients with P. vivax monoinfection will be treated with either weekly or delayed one-week course of primaquine, and the currently recommended by national guideline, 12-week chloroquine regimen to compare treatment safety among groups. All groups will be actively monitored for hemolysis during treatment and will have six-month follow-up period to assess treatment efficacy.
Detailed description
This is an open-label, randomized, phase II, clinical trial of safety and efficacy. Patients will be screened for eligibility and treated at the Fundação de Medicina Tropical Dr Heitor Vieira Dourado in Manaus and the Centro de Pesquisa em Medicina Tropical (Cepem) in Porto Velho, Brazil. A total of 104 vivax malaria patients will be recruited into the study, 52 G6PD deficient (Arm 1) and 52 G6PD normal (Arm 2). Patients with spectrophotometrically-confirmed G6PD deficiency (10-60% of adjusted mean male activity) will be divided into three subgroups of 10 patient each. All arms will receive standard 3-day chloroquine course. Additionally, Arm 1a will receive a delayed course of primaquine for 7 days, starting only at the fifth-day post-chloroquine initiation [ARM HALTED DUE TO SAFETY CONCERNS]. Arm 1b will receive weekly primaquine, once a week, for 8 weeks. Arm 1c will receive prophylactic 12-week course of chloroquine, as recommended by national guidelines for such patients (control group in terms of safety). Arm 2, the control group of efficacy, will receive standard regimen, comprised of 3-day chloroquine plus concomitant 7-day primaquine. All patients will receive directly observed therapy (DOT) and will be closely monitored for clinical parameters and laboratory markers of hemolysis including hemoglobin, methemoglobin, lactate dehydrogenase, haptoglobin, reticulocytes, indirect bilirubin, aspartate aminotransferase, and urinalysis. All groups will be followed for 6 months after treatment to assess relapse rate. Primary endpoint is the tolerability of the regimens defined by hemoglobin fall. Secondary endpoints include treatment failure (relapse during follow-up), frequency of adverse effects, and rate of hemoglobin fall during treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1a: Chloroquine + 5th-day Primaquine | Experimental | Drug: Chloroquine, Drug: Primaquine[ARM HALTED PREMATURELY DUE TO SAFETY CONCERNS] |
| 1b: Chloroquine + 8-week Primaquine | Experimental | Drug: Chloroquine, Drug: Primaquine26 G6PD deficient patients. Directly observed therapy. |
| 1c: Chloroquine + 12-week Chloroquine | Active comparator | Drug: Chloroquine26 G6PD deficient patients. Control group in terms of safety. Directly observed therapy. |
| 2: Standard chloroquine + primaquine | Active comparator | Drug: Chloroquine, Drug: Primaquine52 G6PD normal patients. Control group in terms of efficacy. Directly observed therapy. |
Who may qualify
- Ages
- 6 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Uncomplicated vivax malaria monoinfection
- G6PD deficiency ranging from 10%-60% of adjusted mean male activity
- Baseline hemoglobin >9 g/dL
- Willing to comply with study requirements
Key exclusion criteria (4 listed)
- Pregnancy or breastfeeding
- Comorbidities (hepatopathy and/or nephropathy)
- Use of antimalarials in the previous two weeks or current use of potentially hemolytic drugs
- Any condition which would place the subject at undue risk of hemolysis or interfere with the results of the study, as judged by investigator.
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 |
|---|---|---|
| ChloroquineStandard chloroquine (three days) | Drug | 1a: Chloroquine + 5th-day Primaquine, 1b: Chloroquine + 8-week Primaquine, 1c: Chloroquine + 12-week Chloroquine, 2: Standard chloroquine + primaquine |
| PrimaquineDaily Primaquine (0.5 mg of base/kg/day for seven days) starting only at the fifth day post chloroquine initiation. | Drug | 1a: Chloroquine + 5th-day Primaquine |
| PrimaquineWeekly primaquine (0.75 mg of base/kg/week for eight weeks) starting with first dose of chloroquine. | Drug | 1b: Chloroquine + 8-week Primaquine |
| ChloroquineWeekly, once a week chloroquine (5 mg of base/kg/week for twelve weeks) | Drug | 1c: Chloroquine + 12-week Chloroquine |
| PrimaquineStandard primaquine (0.5mg of base/kg/day for seven days) concomitant with chloroquine. | Drug | 2: Standard chloroquine + primaquine |
Primary outcome
Absolute or relative change in hemoglobin < 3g/dL or 30% from baseline
Time frame: From date of randomization until the date of last dose, assessed up to 12 weeks.
Hemoglobin reduction from baseline after exposure to primaquine for P. vivax treatment
3 secondary outcomes
Regimen efficacy
Time frame: 6 months post treatment
Adverse effects
Time frame: From date of randomization until the date of first documented event, assessed up to 12 weeks.
Change in hemoglobin values over treatment
Time frame: through study completion: before intervention and up to 12 weeks during intervention.
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 20 Feb 2025.
- Derived from this study: PubMed 39785834Barbosa L, Brito-Sousa J, Nascimento C, Pacheco A, Alexandre M, Alencar A, Melo M, Omena A, Souza I, Silva E, Queiroz M, Siqueira V, Rabelo C, Baia-da-Silva D, Silva D, Rocha Y, Barbosa A, Castro R, Almeida A, Brito M, Lopes A, Balieiro A, Costa M, Amaral T, Valle C, Vieira A, Gonzaga J, Pereira D, Alecrim M, Monteiro W, Lacerda M, Melo G. Safety and Efficacy of 3 Alternative Regimens Against Relapsing Plasmodium vivax Malaria in Glucose 6-Phosphate Dehydrogenase-Deficient Patients in the Brazilian Amazon (ALTPRIM). Clin Infect Dis. 2025 Dec 24;81(5):e294-e301. doi: 10.1093/cid/ciaf007.
- Individual participant dataSharing planned: Undecided
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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.
Marcus VG Lacerda, MD, PhD principal investigator
Fiocruz/ILMD and Fundacao de Medicina Tropical Dr Heitor Vieira Dourado
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Chloroquine and Primaquine in people with Vivax Malaria and G6PD Deficiency, run by Fundação de Medicina Tropical Dr. Heitor Vieira Dourado at 2 sites in Brazil.
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 4 inclusion and 4 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 20 Feb 2025. 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 Brazil. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Absolute or relative change in hemoglobin < 3g/dL or 30% from baseline (time frame: From date of randomization until the date of last dose, assessed up to 12 weeks.). 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 NCT03529396, which also lists 1 linked publication.
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 20 Feb 2025.