Efficacy of 3 Regimens of Chloroquine and Primaquine for Treatment of P. Vivax Malaria, Cruzeiro do Sul, Acre, Brazil

NCT ID: NCT03610399

Last Updated: 2021-08-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 257 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-09
• Study Completion Date: 2019-03-12

Brief Summary

We plan to assess the efficacy of 3 different regimens of chloroquine and primaquine for the treatment of P. vivax infections in Cruzeiro do Sul, Acre, Brazil. Patients will be divided in 3 different groups: treatment with regular dose of primaquine (0.5 mg/kg per day for 7 days) with directly observed therapy; regular dose of primaquine without directly observed therapy; and increased total dose of primaquine (0.5 mg/kg per day for14 days) with directly observed therapy. All patients will receive chloroquine (CQ) for three days at a daily dose of approximately 25 mg/Kg in accordance with the Brazilian National Malaria Control guidelines. Clinical and parasitologic parameters will be monitored over a 28-day follow-up period to evaluate drug efficacy and for a total period of 168 days (24 weeks) to evaluate chances of recrudescence, relapse, or reinfection. Results from this drug efficacy study will be used to assist the Brazilian Ministry of Health in assessing their national malaria treatment policy for P. vivax malaria.

Detailed Description

Background: The World Health Organization recommends that antimalarial treatment policies be evaluated every few years to check their efficacy. P. vivax malaria is the most common species in Brazil and cases are concentrated in the Amazon Region in Brazil.

Objectives: Assess the efficacy of 3 different regimens of chloroquine and primaquine for the treatment of P. vivax infections in Cruzeiro do Sul, Acre, Brazil.

Methods: An in vivo drug efficacy study will be conducted in Cruzeiro do Sul, Acre State, Brazil. A total of 257 study participants ≥5 years of age with parasitologically confirmed P. vivax monoinfections will be included. Patients will be divided in 3 different groups: treatment with regular dose of primaquine (0.5 mg/kg per day for 7 days) with directly observed therapy; regular dose of primaquine without directly observed therapy; and increased total dose of primaquine (0.5 mg/kg per day for14 days) with directly observed therapy. All patients will receive chloroquine (CQ) for three days at a daily dose of approximately 25 mg/Kg in accordance with the Brazilian National Malaria Control guidelines. Primaquine will be given for 7 or 14 days under supervision or not, depending on the study group. Clinical and parasitologic parameters will be monitored over a 28-day follow-up period to evaluate drug efficacy and for a total period of 168 days (24 weeks) to evaluate chances of recrudescence, relapse, or reinfection. Blood samples will be taken to measure the CQ levels in blood on Day 7 and day of failure, if occurring in the initial 28 days of follow up. In addition, a blood sample will be collected on filter paper on first day and on day of suspected failure to help differentiate parasite genotypes using techniques based on polymerase chain reaction. Results from this drug efficacy study will be used to assist the Brazilian Ministry of Health in assessing their national malaria treatment policy for P. vivax malaria.

Conditions

P Vivax; Malaria, Vivax

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Primaquine Regular Dose Unsupervised

This is the regular primaquine dose Brazil without directly observed therapy.

Group Type: OTHER

Primaquine

Intervention Type: DRUG

Different total dose and supervision.

Primaquine Regular Dose Supervised

This is the regular primaquine dose in Brazil but with directly observed therapy.

Group Type: ACTIVE_COMPARATOR

Primaquine

Intervention Type: DRUG

Different total dose and supervision.

Primaquine Double Dose Unsupervised

This is the double total primaquine dose (14 days) in Brazil with directly observed therapy.

Group Type: ACTIVE_COMPARATOR

Primaquine

Intervention Type: DRUG

Different total dose and supervision.

Interventions

Primaquine

Different total dose and supervision.

Intervention Type: DRUG

Other Intervention Names

Primaquine dose

Eligibility Criteria

Inclusion Criteria

• 1. Age ≥5 years 2. Body weight <120 kg 3. Documented fever (axillary temperature ≥37.5o C) or history of fever during the previous 48 hours in the absence of another obvious cause of fever, such as pneumonia, otitis media, etc 4. Monoinfection with P. vivax with parasitemia between 100 and 200,000 asexual parasites/µl as determined by microscopic examination of thick and thin peripheral blood smears 5. Informed consent from the patient or parent/guardian (for those <18 years), assent from child (ages 7 to 17 years inclusive), patients 5 through 6 years old will not need an assent 6. Willingness on the part of the patient to return to the clinic and/or receive home visits for regular check-ups during the 24-week (168 days) follow-up period 7. Place of residence within 30-45 minutes of study site.

Exclusion Criteria

• 1. Presence of malaria danger signs

1. Unable to drink

2. Vomiting (more than twice in the previous 24 hours)

3. Recent history of convulsions (one or more in the previous 24 hours)

4. Impaired consciousness

5. Unable to sit or stand 2. Presence of signs of severe malaria (WHO criteria)

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1. Cerebral malaria (unarousable coma)

3. Renal failure (serum creatinine >3 mg/dL or clinical signs)

4. Pulmonary edema

5. Hypoglycemia (blood glucose <40mg/dL or clinical signs)

6. Shock (systolic blood pressure <70 mm Hg in adults; 50 mm Hg in children)

7. Spontaneous bleeding/disseminate intravascular coagulation

8. Repeated generalized convulsions

9. Acidemia/acidosis (clinical signs)

10. Macroscopic hemoglobinuria

11. Jaundice 3. Self-reported presence of other underlying chronic or severe diseases (e.g., cardiac, renal, hepatic diseases, HIV/AIDS, tuberculosis, malnutrition, psoriasis) 4. History of hypersensitivity reactions to any of the drugs being tested. Mild itching with CQ is not in itself a criterion for exclusion. This occurrence will be evaluated by the study doctor before excluding the patient for this reason alone.

• Minimum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, Brazil

OTHER_GOV

Sponsor Role: collaborator

Evandro Chagas National Institute of Infectious Disease

OTHER

Sponsor Role: collaborator

Centers for Disease Control and Prevention

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alexandre Macedo de Oliveira, MD

Role: PRINCIPAL_INVESTIGATOR

Centers for Disease Control and Prevention

Locations

Hospital do Jurua

Cruzeiro do Sul, , Brazil

Countries

Brazil

References

Chamma-Siqueira NN, Negreiros SC, Ballard SB, Farias S, Silva SP, Chenet SM, Santos EJM, Pereira de Sena LW, Povoa da Costa F, Cardoso-Mello AGN, Marchesini PB, Peterka CRL, Viana GMR, Macedo de Oliveira A. Higher-Dose Primaquine to Prevent Relapse of Plasmodium vivax Malaria. N Engl J Med. 2022 Mar 31;386(13):1244-1253. doi: 10.1056/NEJMoa2104226.

Reference Type: DERIVED

PMID: 35353962 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

7061

Identifier Type: -

Identifier Source: org_study_id