Short Course Radical Cure of P. Vivax Malaria in Nepal
Study Details
Study Description
Brief Summary
This study is designed as a multicentre randomized, open label trial to assess the safety and efficacy of a low dose short course PQ treatment (3.5mg/kg total dose given over 7 days) in glucose-6-phosphate dehydrogenase (G6PD) normal patients with P.vivax and P falciparum to reduce the risk of subsequent P.vivax episodes.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Detailed Description
Plasmodium vivax is associated with recurrent infections weeks or months following the acute infection due to reactivation of dormant liver stages. Recurrent infections can be associated with a febrile illness, cumulative risk of severe anaemia, direct and indirect mortality, and are the most important source of onward transmission of the parasite.
In co-endemic areas, there is a very high risk (up to 50%) of patients representing with P.vivax malaria following treatment of P falciparum. Hence, in co-endemic regions there is a strong rationale for eradicating P.vivax hypnozoites from the liver in patients presenting with uncomplicated P. falciparum infections.
The recently completed multicentre IMPROV study compared the efficacy of a 7 day PQ regimen (1.0mg/kg/day for 7 days) with a 14 day regimen (0.5mg/kg/day for 14 days). The 7 day PQ regimen was non-inferior to the 14 day regimen and 5 times more efficacious at reducing P.vivax recurrence than the control.
This study is designed as a multicentre randomized, open label trial to assess the safety and efficacy of a low dose short course PQ treatment (3.5mg/kg total dose given over 7 days) in G6PD normal patients with P.vivax and P falciparum to reduce the risk of subsequent P.vivax episodes.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: (P.f) patients with falciparum malaria will receive artemether-lumefantrine (AL) twice daily over three days plus a low dose course of primaquine (PQ) (3.5mg/kg total dose) given 7 days during schizontocidal treatment |
Drug: primaquine
Primaquine regimen over 7 days (0.5mg/kg/day for 7 days)
Other Names:
|
| Experimental: (P.v) patients with vivax malaria will receive chloroquine (CQ) daily for three days plus a low dose course of PQ (3.5mg/kg total dose) given over 7 days during schizontocidal treatment. |
Drug: primaquine
Primaquine regimen over 7 days (0.5mg/kg/day for 7 days)
Other Names:
|
| No Intervention: Standard care (P.f) patients with falciparum malaria will receive artemether-lumefantrine (AL) twice daily over three days (plus a single dose PQ) |
|
| No Intervention: Standard care (P.v) patients with vivax malaria will receive chloroquine (CQ) daily for three days plus a low dose course of PQ (total dose 3.5mg/kg) over 14 days |
Outcome Measures
Primary Outcome Measures
- Incidence Risk of P. vivax relapse at month 6 [6 months]
The incidence risk of symptomatic P. vivax malaria at month 6 in patients enrolled with P. vivax and P. falciparum infection.
Secondary Outcome Measures
- The incidence risk of symptomatic P. vivax malaria at month 6 in patients enrolled with P. vivax [6 months]
- The incidence risk of symptomatic P. vivax malaria at month 6 in patients enrolled with P. falciparum [6 month]
- The incidence risk of symptomatic P. vivax malaria at day 28 in patients enrolled with P. falciparum and vivax malaria infection [Day 28]
- The incidence risk of all (symptomatic and asymptomatic) P. vivax malaria at day 28 in patients enrolled with P. falciparum and vivax malaria infection [Day 28]
- The incidence risk of asymptomatic P. vivax malaria at day 28 in patients enrolled with P. falciparum and vivax malaria infection [Day 28]
Other Outcome Measures
- The proportion of patients vomiting their medication within 1 hour of administration [1 h]
- The proportion of patients vomiting any of their PQ doses during the supervised course [7 - 14days]
- The proportion of adverse events and serious adverse events [6 month]
- The incidence risk of severe anaemia (Hb<7g/dl) and/or the risk for blood transfusion [6 month]
- Risk of greater than 25% fall in haemoglobin on any day of treatment [7-14days]
- The incidence risk of an acute drop in Hb of >5g/dl during PQ treatment [7-14days]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
- falciparum and/or vivax infection
-
Fever (axillary temperature ≥37.5⁰C) or history of fever in preceding 48 hours
-
Age >1 years
-
G6PD normal by Rapid Diagnostic Test (RDT) as per national guidelines
-
Written informed consent
-
Able to comply with all study procedures and timelines
Exclusion Criteria:
-
General danger signs or symptoms of severe malaria
-
Anaemia, defined as Hb <8g/dl
-
Pregnant women as determined by Urine β-HCG pregnancy test
-
Breast feeding women
-
Known hypersensitivity to any of the drugs given
-
Regular use of drugs with haemolytic potential
-
Blood transfusion within the last 4 months
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Malakheti Hospital | Malakheti | Nepal | ||
| 2 | Tikapur Hospital | Tikapur | Nepal |
Sponsors and Collaborators
- Menzies School of Health Research
- Tribhuvan University, Nepal
Investigators
- Principal Investigator: Kamala Ley-Thriemer, MD, PhD, Menzies School of Health Research
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SIRIN