Clinical trial NCT01775592: Plasmodium Falciparum Artemisinin Resistance Vietnam
Official title: Monitoring the Efficacy of Dihydroartemisinin - Piperaquine in Patients With Uncomplicated Falciparum Malaria in Traleng Commune, Central Vietnam
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Plasmodium Falciparum
Keywords: P.f resistance
Lead sponsor: National Institute of Malariology, Parasitology and Entomology, Vietnam
Sponsor class: OTHER_GOV
Collaborators: name: Institute of Tropical Medicine, Belgium
First posted: 2013-01-25
Enrollment: 95
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Resistance of Plasmodium falciparum toward Artemisinins, the most important drug for the successful treatment of malaria, has been confirmed in Cambodia. There are few reports from neighbouring countries about delayed parasite rates. The investigators therefore aim to assess parasite clearance in malaria patients in central Vietnam when treated according to national standard guidelines.

Detailed description: General objective To evaluate the efficacy of DHA-PPQ in patients with uncomplicated falciparum malaria in a rural area of Central Vietnam, and to assess the in vitro susceptibility of P.falciparum isolates to DHA and PPQ.

Specific objectives

1. To measure the parasite clearance time in falciparum malaria patients treated with DHA-PPQ.
2. To determine the efficacy of DHA-PPQ at day 42 post-treatment.
3. To assess the in vitro susceptibility of P.falciparum isolates towards DHA and PPQ in Quang Nam Province.
4. To compare genetic profiles of P.falciparum isolates with delayed and those with normal clearance times in order to identify potential markers of resistance;

Eligibility criteria: Inclusion Criteria:

* Age: from 6 months of age;
* Fever (body temperature above 37.5C) or history of fever in the previous 24 hours;
* Mono-infection with P.falciparum with parasite density between 500-100,000/µl
* Written informed consent to participate to the trial. For patients aged less than 18 years, an informed consent will be obtained from a parent or a guardian.

Exclusion Criteria:

* Mixed malaria infection;
* Pregnancy or lactation (urine test for β human chorionic gonadotropin to be performed on any woman of child bearing age unless menstruating);
* Concomitant acute illness necessitating specific treatment (antibiotics);
* Underlying chronic severe illness (e.g. cardiac, renal, hepatic diseases, HIV/AIDS).
* Severe malnutrition;
* Danger signs:

  * not able to drink
  * incontrollable vomiting
  * recent history of convulsions (\>1 in 24 hours)
  * unconscious state; neurological impairment
  * unable to sit or stand
* Signs of severe malaria:

  1. Cerebral malaria (unrousable coma)
  2. Severe anaemia (Htc\< 15%)
  3. Renal failure (serum creatinine \> 3 mg/dL)
  4. Pulmonary oedema;
  5. Hypoglycemia (\<40mg/dL)
  6. Shock (systolic BP \< 70 mmHg in adults, 50 in children)
  7. Spontaneous bleeding
  8. Repeat generalized convulsions
  9. Macroscopic haemoglobinuria
  10. Severe jaundice
* Persons who have received quinine, artemisinin or artemisinin derivatives within the last 7 days, 4-aminoquinolines within the last 14 days, pyrimethamine and/or sulfonamides within the last 28 days, or mefloquine within the last 56 days should be excluded from the in vitro testing

Primary outcomes:
measure: Parasite clearance time
timeFrame: Day 2-5
Secondary outcomes:
measure: efficacy of DHA-PPQ at day 42 post-treatment in Traleng Quangnam, Vietnam
timeFrame: Day 42
measure: in vitro susceptibility of P.falciparum isolates towards DHA and PPQ in Quang Nam Province
timeFrame: Day 3-10
Other outcomes:
measure: genetic profiles of P.falciparum isolates with delayed and those with normal clearance times in order to identify potential markers of resistance
timeFrame: 1year
Locations:
city: Tra Leng
country: Vietnam
facility: Health Centre Tra Leng
state: Quang Nam
Study officials:
affiliation: ITM
name: Annette Erhart, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Thriemer K, Hong NV, Rosanas-Urgell A, Phuc BQ, Ha do M, Pockele E, Guetens P, Van NV, Duong TT, Amambua-Ngwa A, D'Alessandro U, Erhart A. Delayed parasite clearance after treatment with dihydroartemisinin-piperaquine in Plasmodium falciparum malaria patients in central Vietnam. Antimicrob Agents Chemother. 2014 Dec;58(12):7049-55. doi: 10.1128/AAC.02746-14. Epub 2014 Sep 15.