Back to results

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

Primary Purpose

P Vivax, Malaria, Vivax

Status

Completed

Phase

Not Applicable

Locations

Brazil

Study Type

Interventional

Intervention

Primaquine

About this trial

This is an interventional treatment trial for P Vivax focused on measuring treatment response, efficacy, primaquine, chloroquine

Eligibility Criteria

5 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)
1. Cerebral malaria (unarousable coma)
2. Severe anemia (hematocrit <15% or clinical signs) hemoglobin <5 mg/ml) (Note: we will use hemoglobin less than 8 mg/ml as exclusion criteria)
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.
  5. Use of drugs with antimalarial activity in the past 30 days. (Annex D) 6. Current pregnancy (either self-reported being pregnant at enrollment or a positive urine or plasma pregnancy test at time of enrollment), previous pregnancy is not an exclusion criteria 7. Hemoglobin <8 mg/mL 8. G6PD deficiency. This will be a late exclusion criteria as soon as the results of G6PD testing becomes available.

Sites / Locations

Hospital do Jurua

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Active Comparator

Arm Label

Primaquine Regular Dose Unsupervised

Primaquine Regular Dose Supervised

Primaquine Double Dose Unsupervised

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Participants With Adequate Clinical and Parasitologic Response Among Patients Enrolled

Participants with adequate clinical and parasitologic response among patients enrolled, meaning patients who did not fail treatment by day 28. Those are participants who at day 28 did not present clinical deterioration or presence of parasitemia.

Participants With Adequate Clinical and Parasitologic Response Among Patients Enrolled

Participants with adequate clinical and parasitologic response among patients enrolled, meaning patients who did not fail treatment by day 168. Those are participants who at day 168 did not present clinical deterioration or presence of parasitemia.

Secondary Outcome Measures

Participants With Adequate Clinical and Parasitologic Response Based on Microsatellite-corrected Analysis Per Protocol Day 168

Participants with microsatellite-corrected adequate clinical and parasitologic response among patients enrolled, meaning patients who did not fail treatment by day 168. Those are participants who at day 168 did not present clinical deterioration or presence of parasitemia with homologous (same genotype) parasites.

Full Information

NCT ID

NCT03610399

First Posted

February 12, 2018

Last Updated

August 5, 2021

Sponsor

Centers for Disease Control and Prevention

Collaborators

Ministry of Health, Brazil, Evandro Chagas National Institute of Infectious Disease

1. Study Identification

Unique Protocol Identification Number

NCT03610399

Brief Title

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

Official Title

Efficacy of Three Regimens of Chloroquine and Primaquine for the Treatment of Plasmodium Vivax Malaria in Cruzeiro do Sul, Acre, Brazil

Study Type

Interventional

2. Study Status

Record Verification Date

June 2021

Overall Recruitment Status

Completed

Study Start Date

April 9, 2018 (Actual)

Primary Completion Date

March 12, 2019 (Actual)

Study Completion Date

March 12, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Centers for Disease Control and Prevention

Collaborators

Ministry of Health, Brazil, Evandro Chagas National Institute of Infectious Disease

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

P Vivax, Malaria, Vivax

Keywords

treatment response, efficacy, primaquine, chloroquine

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

We plan to compare 3 different regimens of primaquine for P. vivax treatment.

Masking

None (Open Label)

Allocation

Randomized

Enrollment

257 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Primaquine Regular Dose Unsupervised

Arm Type

Other

Arm Description

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

Arm Title

Primaquine Regular Dose Supervised

Arm Type

Active Comparator

Arm Description

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

Arm Title

Primaquine Double Dose Unsupervised

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Primaquine

Other Intervention Name(s)

Primaquine dose

Intervention Description

Different total dose and supervision.

Primary Outcome Measure Information:

Title

Participants With Adequate Clinical and Parasitologic Response Among Patients Enrolled

Description

Time Frame

28 days

Title

Participants With Adequate Clinical and Parasitologic Response Among Patients Enrolled

Description

Time Frame

168 days

Secondary Outcome Measure Information:

Title

Participants With Adequate Clinical and Parasitologic Response Based on Microsatellite-corrected Analysis Per Protocol Day 168

Description

Time Frame

168 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

5 Years

Accepts Healthy Volunteers

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 Unable to drink Vomiting (more than twice in the previous 24 hours) Recent history of convulsions (one or more in the previous 24 hours) Impaired consciousness Unable to sit or stand 2. Presence of signs of severe malaria (WHO criteria) Cerebral malaria (unarousable coma) Severe anemia (hematocrit <15% or clinical signs) hemoglobin <5 mg/ml) (Note: we will use hemoglobin less than 8 mg/ml as exclusion criteria) Renal failure (serum creatinine >3 mg/dL or clinical signs) Pulmonary edema Hypoglycemia (blood glucose <40mg/dL or clinical signs) Shock (systolic blood pressure <70 mm Hg in adults; 50 mm Hg in children) Spontaneous bleeding/disseminate intravascular coagulation Repeated generalized convulsions Acidemia/acidosis (clinical signs) Macroscopic hemoglobinuria 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. 5. Use of drugs with antimalarial activity in the past 30 days. (Annex D) 6. Current pregnancy (either self-reported being pregnant at enrollment or a positive urine or plasma pregnancy test at time of enrollment), previous pregnancy is not an exclusion criteria 7. Hemoglobin <8 mg/mL 8. G6PD deficiency. This will be a late exclusion criteria as soon as the results of G6PD testing becomes available.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alexandre Macedo de Oliveira, MD

Organizational Affiliation

Centers for Disease Control and Prevention

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hospital do Jurua

City

Cruzeiro do Sul

Country

Brazil

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

There is not such a plan.

Citations:

PubMed Identifier

35353962

Citation

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.

Results Reference

derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs