Malaria
Conditions
Brief summary
This is a study assessing safety and efficacy of current national guidelines for the treatment of uncomplicated malaria in Bangladesh as well as to assess the G6PD status among the enrolled patients.
Detailed description
The national guidelines for the treatment of uncomplicated malaria in Bangladesh currently recommend a standard dose of artemether-lumefantrine followed by a single dose of primaquine for P. falciparum malaria and a three day course of chloroquine followed by 14 days of primaquine for vivax malaria.Currently the national treatment guidelines do not include any testing for G6PD deficiency before treatment with primaquine. In order to guarantee safe and efficacious treatment for all patients diagnosed with uncomplicated malaria in Bangladesh, it is essential to monitor the effectiveness and safety of the recommended treatment guidelines. This trial therefore evaluates the local efficacy and safety of the current first line treatment and assesses the G6PD status of the enrolled patients. Patients with uncomplicated malaria attending the health care center, who meet the study inclusion criteria will be enrolled, treated on site and followed up for 28 days. The follow-up will consist of a fixed schedule of check-up visits and corresponding clinical and laboratory examinations. The study will provide efficacy data for both artemether-lumefantrine and chloroquine and will generate data on G6PD status in the region, which will provide vital information for policy makers in regards to the wider roll out of primaquine for the radical cure of vivax malaria.
Interventions
DRUGchloroquine
standard dose
standard dose
DRUGPrimaquine
single dose
Sponsors
International Centre for Diarrhoeal Disease Research, Bangladesh
Menzies School of Health Research
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 12 months * P. vivax or P. falciparum monoinfection or P.v. / P.f. mixed infection * Presence of axillary temperature ≥ 37.5°C or history of fever during the past 24 hrs * Ability to swallow oral medication. * Ability and willingness to comply with the study protocol for the duration of the study * Informed consent/assent from the patient or from a parent or guardian in the case of children.
Exclusion criteria
* Presence of general danger signs in children aged under 5 years or signs of severe malaria according to the definitions of WHO * Presence of severe malnutrition * Acute anaemia \<8g/dL * Regular medication, which may interfere with antimalarial pharmacokinetics * History of hypersensitivity reactions or contraindications to any of the drug(s) tested or used as alternative treatment(s) * A positive pregnancy test or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Adverse and Serious Adverse Events Following Unsupervised Primaquine Treatment | during follow up (day 28) | The proportion of adverse and serious adverse events following unsupervised primaquine treatment until day 28 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fractional Change in Hb Between Baseline and Day 9 and 16 | day 0 and 16 | — |
| Proportion of Patients With Anaemia Less Than 8g/dl on Day 2 | on day 2 | — |
| Proportion of Patients With Any Parasitemia on Day 3 After Treatment | day 3 | — |
| Proportion of Patients With Fever on Day 2 After Treatment | day 2 | — |
| Proportion of Patients Receiving Blood Transfusion and With Severe Anaemia (Hb<7g/dl) | day 28 | — |
| Proportion of Patients Adhering to 14 Days of Primaquine Treatment in the Vivax Cohort as Measured by Pill Count | day 16 | — |
| The Distribution of G6PD Activity Measured in U/gHb Among All Malaria Patients | day 0 | — |
| Frequency and Type of Variants of the G6PD Gene Within the Study Population | day 0 or 1 | Frequency and type of variants of the G6PD gene within the study population |
| Recurrence of Parasitaemia Within 16 Days of Follow up | day 16 | — |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chloroquine Primaquine 14days P.vivax malaria patients receiving chloroquine and primaquine 14days as per guidelines
chloroquine: standard dose
Primaquine: 14 days | 55 |
| Artemether-lumefantrine Primaquine 1day P.falciparum malaria patients receiving artemether-lumefantrine combination and primaquine 1day as per guidelines
Artemether-lumefantrine combination: standard dose
Primaquine: single dose | 115 |
| Artemether-lumefantrine Primaquine 14days mixed malaria infection receiving artemether-lumefantrine combination and primaquine 14days as per guidelines
Artemether-lumefantrine combination: standard dose
Primaquine: 14 days | 11 |
| Total | 181 |
Baseline characteristics
| Characteristic | Artemether-lumefantrine Primaquine 14days | Total | Chloroquine Primaquine 14days | Artemether-lumefantrine Primaquine 1day |
|---|---|---|---|---|
| Age, Continuous | 14 years | 20 years | 18 years | 22 years |
| Region of Enrollment Bangladesh | 11 participants | 181 participants | 55 participants | 115 participants |
| Sex: Female, Male Female | 6 Participants | 46 Participants | 19 Participants | 21 Participants |
| Sex: Female, Male Male | 5 Participants | 135 Participants | 36 Participants | 94 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 55 | 0 / 115 | 0 / 11 |
| serious Total, serious adverse events | 0 / 55 | 0 / 115 | 0 / 11 |
Outcome results
Primary
The Proportion of Adverse and Serious Adverse Events Following Unsupervised Primaquine Treatment
The proportion of adverse and serious adverse events following unsupervised primaquine treatment until day 28
Time frame: during follow up (day 28)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chloroquine Primaquine 14days | The Proportion of Adverse and Serious Adverse Events Following Unsupervised Primaquine Treatment | 0 events |
| Artemether-lumefantrine Primaquine 1day | The Proportion of Adverse and Serious Adverse Events Following Unsupervised Primaquine Treatment | 0 events |
| Artemether-lumefantrine Primaquine 14days | The Proportion of Adverse and Serious Adverse Events Following Unsupervised Primaquine Treatment | 0 events |
Secondary
Fractional Change in Hb Between Baseline and Day 9 and 16
Time frame: day 0 and 16
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Chloroquine Primaquine 14days | Fractional Change in Hb Between Baseline and Day 9 and 16 | baseline to day 9 | -2.3 percent change Hb |
| Chloroquine Primaquine 14days | Fractional Change in Hb Between Baseline and Day 9 and 16 | baseline to day 16 | -0.5 percent change Hb |
| Artemether-lumefantrine Primaquine 1day | Fractional Change in Hb Between Baseline and Day 9 and 16 | baseline to day 9 | -7.7 percent change Hb |
| Artemether-lumefantrine Primaquine 1day | Fractional Change in Hb Between Baseline and Day 9 and 16 | baseline to day 16 | NA percent change Hb |
| Artemether-lumefantrine Primaquine 14days | Fractional Change in Hb Between Baseline and Day 9 and 16 | baseline to day 9 | -13.8 percent change Hb |
| Artemether-lumefantrine Primaquine 14days | Fractional Change in Hb Between Baseline and Day 9 and 16 | baseline to day 16 | -8.3 percent change Hb |
Secondary
Frequency and Type of Variants of the G6PD Gene Within the Study Population
Frequency and type of variants of the G6PD gene within the study population
Time frame: day 0 or 1
Population: data were not collected
Secondary
Proportion of Patients Adhering to 14 Days of Primaquine Treatment in the Vivax Cohort as Measured by Pill Count
Time frame: day 16
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chloroquine Primaquine 14days | Proportion of Patients Adhering to 14 Days of Primaquine Treatment in the Vivax Cohort as Measured by Pill Count | 34 Participants |
| Artemether-lumefantrine Primaquine 1day | Proportion of Patients Adhering to 14 Days of Primaquine Treatment in the Vivax Cohort as Measured by Pill Count | NA Participants |
| Artemether-lumefantrine Primaquine 14days | Proportion of Patients Adhering to 14 Days of Primaquine Treatment in the Vivax Cohort as Measured by Pill Count | 7 Participants |
Secondary
Proportion of Patients Receiving Blood Transfusion and With Severe Anaemia (Hb<7g/dl)
Time frame: day 28
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chloroquine Primaquine 14days | Proportion of Patients Receiving Blood Transfusion and With Severe Anaemia (Hb<7g/dl) | 0 participants |
| Artemether-lumefantrine Primaquine 1day | Proportion of Patients Receiving Blood Transfusion and With Severe Anaemia (Hb<7g/dl) | 0 participants |
| Artemether-lumefantrine Primaquine 14days | Proportion of Patients Receiving Blood Transfusion and With Severe Anaemia (Hb<7g/dl) | 0 participants |
Secondary
Proportion of Patients With Anaemia Less Than 8g/dl on Day 2
Time frame: on day 2
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chloroquine Primaquine 14days | Proportion of Patients With Anaemia Less Than 8g/dl on Day 2 | 0 participants with Hb under 8g/dl |
| Artemether-lumefantrine Primaquine 1day | Proportion of Patients With Anaemia Less Than 8g/dl on Day 2 | 2 participants with Hb under 8g/dl |
| Artemether-lumefantrine Primaquine 14days | Proportion of Patients With Anaemia Less Than 8g/dl on Day 2 | 0 participants with Hb under 8g/dl |
Secondary
Proportion of Patients With Any Parasitemia on Day 3 After Treatment
Time frame: day 3
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chloroquine Primaquine 14days | Proportion of Patients With Any Parasitemia on Day 3 After Treatment | 0 participants |
| Artemether-lumefantrine Primaquine 1day | Proportion of Patients With Any Parasitemia on Day 3 After Treatment | 2 participants |
| Artemether-lumefantrine Primaquine 14days | Proportion of Patients With Any Parasitemia on Day 3 After Treatment | 0 participants |
Secondary
Proportion of Patients With Fever on Day 2 After Treatment
Time frame: day 2
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chloroquine Primaquine 14days | Proportion of Patients With Fever on Day 2 After Treatment | 0 Participants |
| Artemether-lumefantrine Primaquine 1day | Proportion of Patients With Fever on Day 2 After Treatment | 0 Participants |
| Artemether-lumefantrine Primaquine 14days | Proportion of Patients With Fever on Day 2 After Treatment | 0 Participants |
Secondary
Recurrence of Parasitaemia Within 16 Days of Follow up
Time frame: day 16
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chloroquine Primaquine 14days | Recurrence of Parasitaemia Within 16 Days of Follow up | 0 Recurrences of Parsitaemia |
| Artemether-lumefantrine Primaquine 1day | Recurrence of Parasitaemia Within 16 Days of Follow up | 0 Recurrences of Parsitaemia |
| Artemether-lumefantrine Primaquine 14days | Recurrence of Parasitaemia Within 16 Days of Follow up | 0 Recurrences of Parsitaemia |
Secondary
The Distribution of G6PD Activity Measured in U/gHb Among All Malaria Patients
Time frame: day 0
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chloroquine Primaquine 14days | The Distribution of G6PD Activity Measured in U/gHb Among All Malaria Patients | 7.82 U/gHb |