Malaria, Vivax, P Vivax
Conditions
Keywords
treatment response, efficacy, primaquine, chloroquine
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.
Interventions
DRUGPrimaquine
Different total dose and supervision.
Sponsors
Ministry of Health, Brazil
Evandro Chagas National Institute of Infectious Disease
Centers for Disease Control and Prevention
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
We plan to compare 3 different regimens of primaquine for P. vivax treatment.
Eligibility
Sex/Gender
ALL
Age
5 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Adequate Clinical and Parasitologic Response Among Patients Enrolled | 28 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Adequate Clinical and Parasitologic Response Based on Microsatellite-corrected Analysis Per Protocol Day 168 | 168 days | 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. |
Countries
Brazil
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Primaquine Regular Dose Unsupervised This is the regular primaquine dose (3.5 mg/kg) Brazil without directly observed therapy.
Primaquine: Different total dose and supervision. | 63 |
| Primaquine Regular Dose Supervised This is the regular primaquine dose (3.5 mg/kg) in Brazil but with directly observed therapy.
Primaquine: Different total dose and supervision. | 96 |
| Primaquine Double Dose Unsupervised This is the double total primaquine dose (14 days) (7.0 mg/kg) in Brazil with directly observed therapy.
Primaquine: Different total dose and supervision. | 95 |
| Total | 254 |
Baseline characteristics
| Characteristic | Primaquine Regular Dose Supervised | Primaquine Double Dose Unsupervised | Total | Primaquine Regular Dose Unsupervised |
|---|---|---|---|---|
| Age, Continuous | 20.3 years | 23.5 years | 22.4 years | 26.5 years |
| Race and Ethnicity Not Collected | — | — | 0 Participants | — |
| Region of Enrollment Brazil | 96 participants | 95 participants | 254 participants | 63 participants |
| Sex: Female, Male Female | 44 Participants | 43 Participants | 115 Participants | 28 Participants |
| Sex: Female, Male Male | 52 Participants | 52 Participants | 139 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 63 | 0 / 96 | 0 / 95 |
| other Total, other adverse events | 0 / 63 | 0 / 96 | 0 / 95 |
| serious Total, serious adverse events | 0 / 63 | 0 / 96 | 0 / 95 |
Outcome results
Primary
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.
Time frame: 28 days
Population: Per-protocol uncorrected analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primaquine Regular Dose Unsupervised | Participants With Adequate Clinical and Parasitologic Response Among Patients Enrolled | 61 participants |
| Primaquine Regular Dose Supervised | Participants With Adequate Clinical and Parasitologic Response Among Patients Enrolled | 88 participants |
| Primaquine Double Dose Unsupervised | Participants With Adequate Clinical and Parasitologic Response Among Patients Enrolled | 90 participants |
Primary
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.
Time frame: 168 days
Population: Per-protocol uncorrected analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primaquine Regular Dose Unsupervised | Participants With Adequate Clinical and Parasitologic Response Among Patients Enrolled | 29 participants |
| Primaquine Regular Dose Supervised | Participants With Adequate Clinical and Parasitologic Response Among Patients Enrolled | 44 participants |
| Primaquine Double Dose Unsupervised | Participants With Adequate Clinical and Parasitologic Response Among Patients Enrolled | 67 participants |
Secondary
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.
Time frame: 168 days
Population: Microsatellite-corrected analysis excludes participants who, during follow-up, presented with heterologous infections (genotype different) or whose genotype could not be determined. This reduced the number of overall participants by 12 for the 'Primaquine Regular Dose Unsupervised' arm; 17 participants in the 'Primaquine Regular Dose Supervised' arm; and 8 participants in the 'Primaquine Double Dose Unsupervised' arm, in comparison to the totals in the Participant Flow section.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primaquine Regular Dose Unsupervised | Participants With Adequate Clinical and Parasitologic Response Based on Microsatellite-corrected Analysis Per Protocol Day 168 | 29 Participants |
| Primaquine Regular Dose Supervised | Participants With Adequate Clinical and Parasitologic Response Based on Microsatellite-corrected Analysis Per Protocol Day 168 | 44 Participants |
| Primaquine Double Dose Unsupervised | Participants With Adequate Clinical and Parasitologic Response Based on Microsatellite-corrected Analysis Per Protocol Day 168 | 67 Participants |