Improving the radical cure of vivax malaria (IMPROV)

• Register: ISRCTN
• Last refreshed on: 27 May 2019
• Main ID: ISRCTN16273289
• Date of registration: 18/07/2016
• Prospective Registration: No
• Primary sponsor: Oxford University
• Public title: Improving the radical cure of vivax malaria (IMPROV)
• Scientific title: Improving the Radical Cure of Vivax Malaria: A Multicentre Randomised Comparison of Short and Long Course Primaquine Regimen (IMPROV)
• Date of first enrolment: 01/07/2014
• Target sample size: 1875
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN16273289
• Study type: Interventional
• Study design: Double-blind three-arm randomised controlled trial (Treatment)
• Phase: Not Applicable

Countries of recruitment

Afghanistan, Ethiopia, Indonesia, Viet Nam

Contacts

• Name: Ric Price

Key inclusion & exclusion criteria

Inclusion criteria:
Participant (or parent/guardian of children below age of consent) is willing and able to give written informed consent to participate in the trial; verbal consent in the presence of a literate witness is required for illiterate patients. In addition, written assent (or verbal assent in the presence of a literate witness for illiterates) from children 12 to 17 years as per local practice.

1. Monoinfection with P. vivax of any parasitaemia in countries which use Chloroquine (CQ) as blood schizontocidal therapy. Mixed infections with P. vivax and P. falciparum can be enrolled in countries which use an artemisinin combination therapy
2. Diagnosis based on rapid diagnostic tests
3. Over 6 months of age
4. Weight 5 kg or greater
5. Fever (axillary temperature 37.5 degrees C) or history of fever in the last 48 hours
6. Able, in the investigators opinion, and willing to comply with the study requirements and follow-up

Exclusion criteria:
1. Female participant who is pregnant, lactating or planning pregnancy during the course of the study
2. Inability to tolerate oral treatment
3. Previous episode of haemolysis or severe haemoglobinuria following primaquine
4. Signs/symptoms indicative of severe/complicated malaria or warning signs requiring parenteral treatment- Haemoglobin concentration less than 9 g/dL
5. Known hypersensitivity or allergy to the study drugs
6. Blood transfusion in last 90 days, since this can mask G6PD deficient status
7. A febrile condition due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration)
8. Presence of any condition which in the judgment of the investigator would place the participant at undue risk or interfere with the results of the study (e.g. serious underlying cardiac, renal or hepatic disease; severe malnutrition; HIV/AIDS; or severe febrile condition other than malaria); coadministration of other medication known to cause haemolysis or that could interfere with the assessment of antimalarial regimens
9. Currently taking medication known to interfere significantly with the pharmacokinetics of primaquine and the schizontocidal study drugs
10. Prior antimalarial medications in the previous 7 days


Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

P. vivax malaria
Infections and Infestations
P. vivax malaria

Intervention(s)

Patients will be randomly assigned to one of the three treatment arms below:

Intervention group 1: Standard blood schizonticidal therapy plus 14 days of supervised primaquine (7mg/kg total dose) administered once per day (0.5 mg/kg) orally
Intervention group 2: Standard blood schizonticidal therapy plus 7 days of supervised primaquine (7mg/kg total dose) administered once per day (1.0 mg/kg OD) followed by 7 days of placebo orally
Control group: Standard blood schizintocidal therapy plus 14 days placebo orally

The schizintocidal consists of Chloroquine in Vietnam and Afghanistan, and Dihydroartemisinin-piperaquine in Indonesia.

For all study arms, follow up is daily for 2 weeks, then weekly till week 8 and then monthly until 12 months.

Primary Outcome(s)

1. Incidence rate (per person-year) of symptomatic recurrent P. vivax is measured within 12 months
2. Incidence rate (per person-year) of symptomatic recurrent P. vivax parasitaemia (detected by microscopy) over 12 months of follow-up in the 7 versus 14-day primaquine groups for all sites combined and stratified by site

Secondary Outcome(s)

1. The incidence rate (per person-year) of any recurrent P. vivax malaria is measured at 12 months
2. The incidence rate (per person-year) of any recurrent (i.e. symptomatic and asymptomatic) P. vivax parasitaemia over 12 months of follow-up in the 7 and 14-day primaquine regimens for all sites combined and stratified by site
3. Incidence risk of any recurrent symptomatic of P. vivax malaria compared to control arm is measured at 12 months
4. The incidence rate (per person-year) of any recurrent symptomatic P. vivax parasitaemia over 12 months of follow-up in either the 7 or the 14-day primaquine regimens compared with the control arm, for all sites combined and stratified by site
5. The Haematological recovery in patients with vivax malaria will be assessed as the incidence risk of severe anaemia (Hb<7g/dl) and/or blood transfusion within the 12 month follow up period, and the mean fall in baseline Hb at day 7 and day 14
6. Proportion of patients with Serious Adverse Drug reactions is measured within 42 days of primary treatment, 6 and 12 months
7. Tolerability of primaquine will be assessed by comparing the proportion of patients with nausea, vomiting, abdominal pain and vomiting of a dose within 1 hour of administration within 12 months
8. Drug tolerability will be assessed by comparing the proportion of patients completing a full course of observed primaquine therapy within 12 months
9. Incidence risk of severe anaemia in G6PD deficient arm and/or requirement for blood transfusion within the 12 month follow up period and the mean fall in baseline Hb at day 7 and day 14
10. Cost effective analysis in the management of P. vivax with respect to the use of G6PD tests, the dosing schedule and the epidemiological context will be conducted at 12 months

Secondary ID(s)

NCT01814683

MR/K007424/1

Source(s) of Monetary Support

Medical Research Council, Bill and Melinda Gates Foundation

Secondary Sponsor(s)

Menzies School of Health Research

Ethics review

Status:
Approval date:
Contact:

1. Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research (HREC), 16/06/2013, ref: 2013-1991 2. Oxford Tropical Research Ethics Committee (OxTREC), 04/06/2013, ref: 1014-13

Results

• Results available: Yes
• Date Completed: 28/02/2018