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P. Falciparum Resistance to Artemisinin in Vietnam

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ClinicalTrials.gov Identifier: NCT02604966
Recruitment Status : Unknown
Verified October 2015 by National Institute of Malariology, Parasitology and Entomology, Vietnam.
Recruitment status was:  Recruiting
First Posted : November 16, 2015
Last Update Posted : December 21, 2015
Sponsor:
Collaborator:
Institute of Tropical Medicine, Belgium
Information provided by (Responsible Party):
National Institute of Malariology, Parasitology and Entomology, Vietnam

Brief Summary:

At the end of 2012, the Institute of Tropical Medicine in collaboration with National Institute of Malariology Parasitology and Entomology (NIMPE) conducted a study in Quang Nam province, central Vietnam, to assess the efficacy of the national DHA-PPQ regimen for the treatment of uncomplicated P. falciparum malaria infections, both in adults and in children. Results showed that about 30% of the study participants were parasitaemic at day 3. Parasite clearance rate was estimated at 6.2h, which was comparable to figures from Pailin, Cambodia, where artemisinin resistance were previously reported . However, results from this study have to be interpreted bearing in mind that: (i) the age-based drug dosing scheme used has been criticized as insufficient to clear parasites and (ii) DHA-PPQ drugs used (Artecan™), Vietnam, are not produced under Good Manufacturing Practices (GMPs). However, those results prompted the NMCP and WHO to declare Quang Nam, Binh Phuoc, Dak Nong, and Gia Lai provinces as a "Tier I area" (credible evidence of artemisinin resistance) in May 2013. By end of 2014 a fifth province, Khanh Hoa, was declared Tier I (Dr Hong, Personal Communication). Except for the south-eastern province of Binh Phuoc, artemisinin resistance has never been confirmed with an artemisinin based monotherapy in Central Vietnam.

Therefore, in order to confirm artemisinin resistance in Central Vietnam , a study with oral artemisinin-based monotherapy, using WHO prequalified AS and DHA-PPQ and recommended dosing scheme of 4mg/kg/day for AS and DHA, is needed. In the arm where study participants are treated with 3 days of AS monotherapy, treatment will be followed by an additional 3-day course of DHA-PPQ to effectively clear all parasites.

The aim of the present study is to confirm artemisinin resistance in Central Vietnam by assessing P. falciparum clearance time and rate after AS monotherapy (WHO recommended dosage). The investigators will conduct a two-arm open label, randomized study, with one arm receiving AS monotherapy for 3 days + 3-day of DHA-PPQ, and a second arm receiving 3 days of DHA-PPQ.


Condition or disease Intervention/treatment Phase
Drug Resistant Malaria Due to Plasmodium Falciparum Drug: Artesunate (AS) group Drug: DHA - PPQ group Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy of Artesunate Monotherapy and Dihydroartemisinin - Piperaquine in Patients With Uncomplicated Falciparum Malaria in Central Vietnam
Study Start Date : April 2015
Estimated Primary Completion Date : September 2016
Estimated Study Completion Date : December 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Experimental: Artesunate (AS) group
P. falciparum infected patients randomly allocated to this arm will be treated with AS (50mg/tablet) 4 mg/kg body weight once daily for three days followed by DHA-PPQ (40mg of DHA +320mg of PPQ/tablet) once daily for three days.
Drug: Artesunate (AS) group
Oral treatment with AS at 4mg/kg/day for 3 days followed by three days of DHA - PPQ in order to insure total parasite clearance. Randomization is done by blocks of ten.
Other Name: AS group

Active Comparator: DHA - PPQ group
P. falciparum infected patients randomly allocated to this arm will be treated with the combination DHA-PPQ (40mg of DHA +320mg of PPQ/tablet) once daily for three days.
Drug: DHA - PPQ group
Oral treatment with 3-day course of DHA - PPQ. Randomization is done by blocks of ten.




Primary Outcome Measures :
  1. Median parasite clearance time after treatment with Artesunate or with DHA - PIP [ Time Frame: From time of first treatment dose (day0 hh-mm) until day and time of parasite clearance (=two consecutive blood samples are found negative for parasites) assessed up day 42 ]
    Median parasite clearance time (total hours) in both arms (by light microscopy (LM) and quantitative real time PCR (qPCR)) will be computed using the 12-hourly parasite density measurements from day0 till parasite clearance. Parasite clearance time (in hours) will be computed using the Parasite Clearance Estimator tool available online (http://www.wwarn.org/toolkit/data-management/parasite-clearance-estimator).


Secondary Outcome Measures :
  1. Number of patients with Adequate Clinical and Parasitological Response (ACPR) to DHA-PPQ for the treatment for uncomplicated P falciparum malaria infections in central Vietnam. [ Time Frame: From day0 to day 42 ]
    This outcome is measured at day 28 and 42 of follow-up. Treatment outcomes such as ACPR, early or late clinical failures are defined following WHO guidelines;


Other Outcome Measures:
  1. Ex vivo susceptibility of P. falciparum isolates to AS, DHA , PPQ and CQ (Mean IC50 and IC90) [ Time Frame: At day0 and day of recurrence of P.falciparum parasitemia after initial clearance assessed up to day 42 ]
    Individual and mean IC50 and IC90 values will be computed for each drug using the IVART tool available online (http://www.wwarn.org/tools-resources/toolkit/analyse/ivart)

  2. Number of patients carrying asexual and sexual parasites during 42 days follow up [ Time Frame: From day0 to day 42 ]
    asexual and sexual parasite forms will be detected by quantitative qPCR and reverse transcription real time PCR (rtPCR), respectively. This outcome will be measured for each sampling time point.

  3. Number of patients with parasites carrying molecular markers of Plasmodium falciparum resistance to artemisinins. [ Time Frame: From day 0 to day42 ]
    All parasites at day0, and day3 for patients with delayed clearance, will be genotyped for molecular markers of artemisinin resistance (K13 mutations) following a published protocol.



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Ages Eligible for Study:   1 Year and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Mono-infection with P. falciparum;
  • Parasite density (trophozoites) between 500-100,000/µl;
  • Fever (axillary temperature 37.5C) or history of fever in the previous 24h.;
  • Ability to swallow oral medication;
  • Ability and willingness to comply with the study protocol and with the study visit schedule;
  • Written informed consent/assent to participate to the trial.

Exclusion Criteria:

  • Mixed or mono-infection with another Plasmodium species confirmed by microscopy;
  • General danger signs or symptoms of severe malaria according to WHO definitions;
  • Signs or symptoms of severe malnutrition (weight-for-age ≤ 3 standard deviations below the mean (NCHS/WHO normalized reference values));
  • Anaemia (Hb <7g/dl in adults (<5g/dl in children));
  • Pregnancy or lactation (urine test for β HCG);
  • Concomitant acute illness necessitating specific treatment (antibiotics);
  • Underlying chronic severe illness (e.g. cardiac, renal, hepatic diseases, HIV/AIDS);
  • Known hypersensitivity to any of the drugs being evaluated;
  • Regular use of medication that may interfere with antimalaria pharmacokinetics

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02604966


Contacts
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Contact: Phuc Bui, MD, PhD +84 913522 874 phucnimpe@yahoo.com
Contact: Duong Tran, MD , PhD +84916895919 tranthanhduong@hotmail.com

Locations
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Vietnam
Chu R Cam commune Recruiting
Pleiku, Gialai, Vietnam
Contact: Phuc Bui, MD, PhD    +84913522874    phucnimpe@yahoo.com   
Contact: Hong Nguyen, MD    +841668188919    nvhong1982@yahoo.com   
Sub-Investigator: Annette Erhart, MD, PhD         
Sub-Investigator: Edu Rovira - Vallbona, PhD         
Sponsors and Collaborators
National Institute of Malariology, Parasitology and Entomology, Vietnam
Institute of Tropical Medicine, Belgium
Investigators
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Principal Investigator: Duong Tran, MD, PhD National Institute of Malariology, Parasitology and Entomology, Hanoi, Vietnam
Principal Investigator: Anna Rosanas-Urgell, MD, PhD Institute of Tropical Medicine, Antwerp, Belgium

Publications:

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Responsible Party: National Institute of Malariology, Parasitology and Entomology, Vietnam
ClinicalTrials.gov Identifier: NCT02604966     History of Changes
Other Study ID Numbers: NIMPE - ITM- P.f
First Posted: November 16, 2015    Key Record Dates
Last Update Posted: December 21, 2015
Last Verified: October 2015

Keywords provided by National Institute of Malariology, Parasitology and Entomology, Vietnam:
P. falciparum
resistance to artemisinin
Central Vietnam

Additional relevant MeSH terms:
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Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Artesunate
Artemisinins
Artemisinine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Antineoplastic Agents
Antiviral Agents
Schistosomicides
Antiplatyhelmintic Agents
Anthelmintics