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Malaria, VivaxPhase 3CuraVivaxNCT03208907

DHA-PQP vs Chloroquine and Primaquine for Radical Cure of Vivax Malaria in Brazil

A Phase 3 study testing CQ coadministered with PQ, DHA-PQP coadministered with PQ and CQ and PQ starting on Day 42 in people with Malaria, Vivax and Therapeutics, run by Fundação de Medicina Tropical Dr. Heitor Vieira Dourado at 1 site in Brazil.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Plasmodium vivax can be cause of severe malaria and mortality. There are serious public health implications associated with cases of P. vivax resistant to Chloroquine in the Americas as well there are efforts of many countries to eliminate this disease. Read more about this study

Who is it for?
Ages 6 months and older
Conditions the study is for
Malaria, Vivax, Therapeutics
What is being tested?
CQ coadministered with PQ, DHA-PQP coadministered with PQ and CQ and PQ starting on Day 42
Could I receive a placebo?
No, everyone receives an active treatment
How many people
419 participants
Where
1 siteBrazil
Study dates
5 Jul 2018to 2 Jul 2021
Phase
Phase 3
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

1 Inclusion criteria:

  1. Adults and children over 6 months old (bodyweight>5 kg)
  2. Body weight ≥5 kg and <100 kg (or above, upon justification of the investigator);
  3. Biologically confirmed symptomatic Monoinfection by Plasmodium vivax, with parasite density between 100 and 100,000;
  4. Efficient activity of the enzyme Glucose-6-Phosphate Dehydrogenase (G6PD);
  5. Conditions for oral treatment;
  6. Plans known to remain in the area of the research center during the follow-up period (180 days);
  7. Hemoglobin concentration (Hb) at baseline> 7g / dL.
  8. Women with reproductive potential (defined as women who are not in postmenopausal dust for at least 24 consecutive months, ie without menstruation within 24 months of admission to the study, and women who have not undergone surgical sterilization, specifically hysterectomy or bilateral oophorectomy) must have a negative pregnancy test or urine test within 48 hours prior to admission to the study; NOTE: The history reported by the participant is considered acceptable documentation of hysterectomy, bilateral oophorectomy, and menopause. Women are considered menopausal if they have not had a menstrual period for at least 12 months and have had a follicle-stimulating hormone (FSH) greater than 40 IU/L; if the FSH test not available, they must be in amenorrhea for 24 or more consecutive months. For women of child-bearing age, provision is made for using contraceptives as described in research product and primaquine information. Contraceptives should preferably be used at least two weeks prior to the start of study drug and continued for least one week after the discontinuation of any drug from the study. In case the patient reports that she has not used any contraceptive method in the two weeks prior to inclusion, she may be included if the doctor discards the possibility of pregnancy;
  9. If the patient engage in sexual activity that could lead to pregnancy, women should use a form of contraception. At least one of the following methods should be used properly:

Condoms (male or female) with or without spermicidal agent; Diaphragm or cervical cap with spermicide Intrauterine device (IUD) Hormonal contraceptive Ligation Tubal microimplants i. Women with no reproductive potential, as defined above, are without the use of contraceptives.

  1. Ability and willingness of the participant or legal guardian to provide free and informed consent in writing. Children who are able to understand the goals and risks of the study will sign a consent form.
  2. Non-inclusion criteria:
  3. Participate in another ongoing clinical trial; b. Signs of severe malaria such as: recent history of seizures (1-2 within 24 hours), unconscious state, lethargy, inability to drink or breastfeed, constant vomiting, inability to get up / sit due to weakness; c. Known hypersensitivity to any of the experimental medicinal products or to any of the excipients d. Evidence or report of ingestion of antimalarial treatment in the 60 days prior to inclusion; e. Concomitant or underlying serious illness, such as porphyria or psoriasis or known disturbances of electrolyte balance, such as hypokalemia or hypomagnesemia; f. Liver function test with ALT> 3x the reference value, which, according to the researcher's assessment, endangers the safety of the participant;
  4. Exclusion criteria:
  5. Withdrawal of consent;
  6. The researcher's opinion, based on the risk and benefit assessment of the study;
  7. Detection of mixed infection by malaria;
  8. Women who become pregnant by the 63rd day of follow-up;
  9. Women of childbearing age who give up using effective contraception during the first 63 days of follow-up study;
  10. Discontinuation of blood schizonticidal treatment for any reason.

Trial locations and contacts

1 site in 1 country.

Brazil1 site
  • Fundação de Medicina Tropical Dr. Heitor Vieira Dourado

    Manaus, Amazonas, 69040000

Other trials in Brazil

About this study

Official title: An Open Label Randomized Comparative Study to Assess the Efficacy and Tolerability of Eurartesim® Versus Chloroquine and Nonrelapse Therapy With Primaquine for Uncomplicated Plasmodium Vivax Monoinfection Malaria

Plasmodium vivax can be cause of severe malaria and mortality. There are serious public health implications associated with cases of P. vivax resistant to Chloroquine in the Americas as well there are efforts of many countries to eliminate this disease. In this way, it is critically important to evaluate an alternative radical cure treatment efficient to amazon scenario. The objectives of this trial are to demonstrate the superiority of adequate parasitological response at D42 of Dihydroartemisinin plus Piperaquine (DHA-PQP or Eurartesim®) versus Chloroquine and to evaluate the proportion of failure until D180 considering different starting days of Primaquine (0.50 mg/kg/day) for 14 days. It is an open, 4 arms, randomised, comparative trial. Total of 460 patients are initially planned to be included. To demonstrate the superiority of DHA-PQP compared to Chloroquine, the 95% confidence interval of the difference observed between both treatment success rates will be determined. Each recurrence will be passively and actively detected for 180 days.

Read the detailed description

Dihydroartemisinin/Piperaquine (DHA-PQP or Eurartesim®) is recommended by World Health Organization Expert Board for the treatment of P.vivax malaria, in case of chloroquine-resistance (CQR). However, no clinical study has been conducted to assess the efficacy of DHA-PQP in P.vivax malaria in the Americas. According a study performed in Amazonas state, Brazil, Artesunate/Amodiaquine (ASAQ) exhibited high efficacy against CQ resistant Plasmodium vivax and is an adequate alternative in the study area. They recommend other studies with an efficacious comparator, longer follow-up and genotype-adjustment can improve CQR characterization. Other publication, a meta-analysis of randomized controlled trials, found nine publications from January 1989 to May 2013 in which DHA-PQP was more efficacious than CQ and Artemether/Lumefantrine in treating uncomplicated P. vivax malaria. However, this drug combination is not active against the hypnozoite stage of P. vivax. So, more efforts are required to establish how best combine this treatment with appropriate nonrelapse therapy.

In 2015, primaquine was assessed in high dose for 14 days as treatment for the hypnozoite forms with DHA-PQP or artesunate-pyronaridine (AS-PYR). Both the treatment arms offer evidence of good tolerability and efficacy.

In other previous study performed in an area with high chloroquine-resistance (Southern Papua, Indonesia), DHA-PQP was compared to ASAQ, but never compared to chloroquine by itself in areas where chloroquine still works. The objectives of this trial are to demonstrate the superiority of adequate parasitological response at D42 of Dihydroartemisinin plus Piperaquine versus Chloroquine and to evaluate the proportion of failure until D180 considering different starting days of Primaquine (0.50 mg/kg/day) for 14 days.

This clinical trial will be undertaken in the Amazonas State (Western Brazilian Amazon), in Manaus, at Fundação de Medicina Tropical Dr Heitor Vieira Dourado. The climate is tropical, with mean temperatures between 26°C and 30°C. It is a prospective, open-label, 4-arm, randomized and comparison trial. One hundred and fifteen (115) patients were planned to be enrolled in each treatment arm (after a preliminary analysis this number was increased to 184; total number of participants: 563). In this protocol, all the subjects will be screened to evaluate Glucose-6-phosphate dehydrogenase deficiency (G6PD) deficiency and the laboratorial tests (specially haemoglobin) in all the visits will be evaluated, as well. The referred deficiency is estimated to be 3% among men from the Amazon and essentially the A-type (african type), which leads to moderate deficiency and minor clinical complications. Each dose of the schizonticidal treatment will be administered by a study pharmacist, and the patient will be monitored for 30 minutes after administration. The assessment schedule will be done in days 1, 2, 3, 5, 7, 14, 21, 28, 42, 63, 90, 120, 150 and 180 (in addition, patient will be asked to come back to the health centre if fever occurs at any time).

Being tested
CQ coadministered with PQ, DHA-PQP coadministered with PQ, CQ and PQ starting on Day 42, DHA-PQP and PQ starting on Day 42
Keywords
Vivax malaria, Radical cure, Elimination
Medical subject headings
Malaria, Vivax

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CQ coadministered with PQDrug

    Also called Standard treatment with potential synergy

    113 subjects in a 3-day regimen treatment with the schizonticidal drug Chloroquine concomitantly to 14-day regimen treatment with Primaquine in a dose of 0.50 mg/kg/day.

  • DHA-PQP coadministered with PQDrug

    Also called Experimental treatment with potential synergy

    In this treatment group, 112 subjects took DHA-PQP for three days and Primaquine for 14 days in the following dose: 0.50 mg/kg/day.

  • CQ and PQ starting on Day 42Drug

    Also called Standard treatment with no potential synergy

    98 subjects in a 3-day regimen treatment with Chloroquine with a 14-day regimen treatment with Primaquine in a dose of 0.50 mg/kg/day starting on Day 42 after first dose of the schizonticidal drug.

  • DHA-PQP and PQ starting on Day 42Drug

    Also called Experimental treatment with no potential synergy

    95 subjects in a 3-day regimen treatment with DHA-PQP with a 14-day regimen treatment with Primaquine in a dose of 0.50 mg/kg/day starting on Day 42 after first dose of the schizonticidal drug.

Study groups in NCT03208907
Study groupRoleWhat they receive
CQ coadministered with PQActive comparatorChloroquine was administered for 3 days according to the brazilian protocol and Primaquine was administered for 14 days (0.50mg/kg/day)
Receives: Drug: CQ coadministered with PQ
DHA-PQP coadministered with PQExperimentalDihydroartemisinin/Piperaquine was administered according to the weight and Primaquine (0.50mg/kg/day)
Receives: Drug: DHA-PQP coadministered with PQ
CQ and PQ starting on Day 42ExperimentalChloroquine was administered for 3 days according to the brazilian protocol and Primaquine started on Day 42 for 14 days (0.50mg/kg/day) [arm halted after preliminary analysis]
Receives: Drug: CQ and PQ starting on Day 42
DHA-PQP and PQ starting on Day 42ExperimentalDihydroartemisinin/Piperaquine was administered for 3 days according to the weight and Primaquine started on Day 42 for 14 days (0.50mg/kg/day) [arm halted after preliminary analysis]
Receives: Drug: DHA-PQP and PQ starting on Day 42

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with negative parasitological test (schizonticidal therapy evaluation)

    Schizonticidal efficacy will be assessed based on the absence of Vivax Plasmodium parasites in blood of the participants, confirmed by microscopy.

    Measured: Day 42

  2. Number of participants with negative parasitological test (nonrelapse therapy evaluation)

    Nonrelapse therapy efficacy will be assessed based on the absence of Vivax Plasmodium parasites in blood, confirmed by microscopy.

    Measured: Day 180

Secondary outcomes (4)
  1. Number of participants with negative parasitological test

    Therapy efficacy will be assessed based on the presence or absence of Vivax Plasmodium parasites in blood, confirmed by the presence or absence of parasites in peripheral blood by microscopy.

    Measured: 6 months (for this analysis will not be considered the primary outcomes dates (Day42 and D180)

  2. Number of participants with any biological intolerability

    Evolution of haemoglobin levels until D28 will be monitored in all the scheduled visits and also on unscheduled visits.

    Measured: Until Day 28

  3. Number of participants with any treatment-related adverse event of clinical tolerability

    The participants will be clinically monitored. In all the scheduled visits a study physician will evaluate and register the clinical exam, and also obtain and update the clinical history to describe any adverse event. The participants will have also a card with a 24h phone number to contact in case of clinical symptoms or others needing.

    Measured: 6 months

  4. Number of participants with treatment-related prolonged QT interval.

    Electrocardiogram evaluation will be assessed after completion of schizonticidal treatment

    Measured: Day 3

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jul 2017
  2. Study start5 Jul 2018
  3. Primary completion2 Jul 2021
  4. Study completion2 Jul 2021

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
419 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03208907
Sponsor's protocol ID
CAAE: 69476017.3.0000.0005
Acronym
CuraVivax
Status last verified
Jun 2023
First submitted
30 Jun 2017
Last updated
12 Jun 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Baia-da-Silva DC, Machado KVA, Rabelo ALR, da Silva Balieiro AA, Barbosa ASL, Costa MRF, Sampaio VS, Melo GC, Alexandre MAA, Alencar ACC, Nascimento CT, Jeronimo CMP, Marcovski MS, Barbosa LRA, Valle CS, Carrilho TAA, Vieira JLF, de Melo MM, Dinelly KMO, Omena AG, Brito-Sousa JD, Barreiros GA, Rocha YV, Filho ACA, Bassat Q, Alecrim MDGC, Siqueira AM, Lacerda MVG. Dihydroartemisinin-piperaquine versus chloroquine for the treatment of uncomplicated Plasmodium vivax malaria with concurrent or delayed high-dose primaquine in Brazil (Curavivax): an open-label, single-centre, randomised clinical trial. Lancet Infect Dis. 2026 May 11:S1473-3099(26)00139-8. doi: 10.1016/S1473-3099(26)00139-8. Online ahead of print.

    PubMed 42114535

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing CQ coadministered with PQ, DHA-PQP coadministered with PQ and CQ and PQ starting on Day 42 in people with Malaria, Vivax and Therapeutics, run by Fundação de Medicina Tropical Dr. Heitor Vieira Dourado at 1 site in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

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 12 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

Number of participants with negative parasitological test (schizonticidal therapy evaluation) (time frame: Day 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 NCT03208907, 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 12 Jun 2023.

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