A Randomized Controlled Trial on Malaria Primaquine Treatment in Timika, Indonesia (TRIPI)

Study Overview
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Brief Summary
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Plasmodium vivax can form dormant liver stages that reactivate weeks or months following an acute infection. Recurrent infections can be associated with a febrile illness, a cumulative risk of severe anaemia, and even mortality. In co-endemic areas the risk of recurrence after both P. vivax and P. falciparum infections can be over 50% within 3 months. The only drug we have to kill P. vivax hypnozoites is primaquine which is currently given as a 14 day regimen. In Papua a retrospective study found very low effectiveness for unsupervised treatment. If true this has profound effects on treatment policy, suggesting that greater efforts are needed to encourage adherence to treatment. We propose a cluster randomized, controlled, open label trial to assess the effectiveness of unsupervised versus supervised primaquine treatment in patients with uncomplicated malaria. Since the risk of recurrent P. vivax is high in patients with either P. vivax or P. falciparum, both infections will be included in the study. The study will be conducted in Mimika, in the southern part of Papua Province, Indonesia. Participants will be enrolled at village health posts and provided with schizontocidal treatment plus primaquine radical cure which will be either supervised or unsupervised depending on which cluster the clinic is in. Participants will be followed up for 6 months and assessed in regular intervals for the presence of patent and sub-patent malaria. The outcome of the study will contribute to an improved treatment scheme for uncomplicated malaria in this area.

Official Title
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A Randomized Controlled Trial on Malaria Primaquine Treatment in Timika, Indonesia (TRIPI)

Conditions
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Uncomplicated Malaria

Intervention / Treatment
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* Drug: PQ supervised
* Drug: PQ unsupervised


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infection with Plasmodium falciparum or P. vivax either alone or mixed Age >12 months Weight >5kg Living in the study clusters Exclusion Criteria: General danger signs or symptoms of severe malaria Anaemia, defined as Hb <9g/dl G6PD deficiency (as determined by FST) Pregnant women as determined by Urine β-HCG pregnancy test Known hypersensitivity to any of the drugs given

Ages Eligible for Study
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Minimum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Primaquine supervised<br>14 days of supervised primaquine treatment (0.5mg/kg/day). | Drug: PQ supervised<br> <br> |
| Active Comparator: Primaquine unsupervised<br>14 days of unsupervised primaquine treatment (0.5mg/kg/day). | Drug: PQ unsupervised<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence risk of symptomatic P. vivax malaria over 6 months in patients enrolled with any malaria infection |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence risk of symptomatic P. vivax malaria over 6 months in patients enrolled with P. vivax malaria infection |  | 6 months | 
| The incidence risk of symptomatic P. vivax malaria over 6 months in patients enrolled with P. falciparum malaria infection |  | 6 months | 
| The incidence rate of symptomatic P. vivax malaria over 6 months in patients enrolled with malaria due to P. falciparum or P. vivax |  | 6 months | 
| The incidence rate of symptomatic P. vivax malaria over 6 months in patients enrolled with P. vivax malaria |  | 6 months | 
| The incidence rate of symptomatic P. vivax malaria over 6 months in patients enrolled with P. falciparum malaria |  | 6 months | 
| The incidence risk of patent or sub-microscopic P. vivax malaria over six months in patients enrolled with a malaria (sub-group analysis for patients recruited with P. vivax infection and P. falciparum infection) |  | 6 months | 
| The incidence risk of any patent or sub-microscopic parasitaemia due to P. vivax or P. falciparum over six months in patients |  | 6 months | 
| The proportion of patients vomiting their medication within 1 hour of administration |  | 1 hour | 
| • The proportion of patients vomiting any of their primaquine doses during the 14 day supervised course |  | 14 days | 
| • The proportion of adverse events and serious adverse events over 6 months in all patients |  | 6 months | 
| • The incidence risk of severe anaemia (Hb<7g/dl) and/or the risk for blood transfusion over 6 months |  | 6 months | 
| • The incidence risk of an acute drop in Hb >5g/dl within 14 days of starting primaquine treatment |  | 14 days |