Evaluating the Efficacy of Chloroquine for the Treatment of Plasmodium Vivax Infections in Central Vietnam

NCT02610686 | Unknown Phase 4

• 1 other identifier: ITM- NIMPE
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Understanding the extent and regional distribution of CQR vivax malaria and detecting early signs of resistance is critical to prevent the spread of resistant strains, optimize treatment guidelines, and reduce the risk of recurrent and severe malaria. In Vietnam, CQR in P.vivax has been reported sporadically. One study carried out in Binh Thuan province (central-south Vietnam) at the end of the 1990s demonstrated early P.vivax recurrences (7%) by Day 16 after a 3-day CQ treatment. However, in a summary report to World Health Organization (WHO) including data from 11 sentinel sites, from studies conducted between 2006 and 2011 in central and southern Vietnam (total 350 patients), P.vivax is still considered sensitive to CQ. More recently in a cohort study conducted in Quang Nam province (Central Vietnam) in which P.vivax patients were treated radically with CQ and primaquine (10-day at 0.5mg/kg/day) following national guidelines, the 28-day failure rate was measured at 3.45% and CQ blood concentrations measured at day of recurrence (\>100ng/ml) confirmed resistance in three patients. The current national guidelines for the radical cure regimen of P.vivax infections recommends 3 days of CQ (total 25 mg/kg body weight (bw)) together with 14 days of primaquine at 0.25 mg/kg bw/ day. The current WHO protocol recommends a 28-day follow-up to assess the efficacy of CQ for the treatment of P.vivax infections. However, recurrence of early stage resistant parasites may occur after Day 28 in the presence of CQ blood levels above the minimum efficacy concentration (MEC, ≥100ng/ml) and relapses could occur as early as 36 days after standard CQ treatment. Therefore, in order to confirm CQR it is recommended to extend the follow-up period, to Day 42 or 63 and measure whole blood CQ level at Day 28 and at the time of recurrence. Moreover, it has been shown that emerging drug resistance in P.vivax is associated with delayed parasite clearance after treatment, i.e. some parasites are still detectable at Day 3. The aim of the present study is to assess the in vivo and ex vivo susceptibility of P.vivax to CQ in Central Vietnam following the currently recommended radical cure regimen and using GMP certified CQ.

Conditions

Plasmodium Vivax

Keywords

Plasmodium vivax; recurrence; drug resistance

Outcome Measures

Primary Outcomes (1)

• Number of patients with Adequate Clinical and Parasitological Response (ACPR) at day 42 after treatment with Chloroquine.

  This outcome will be measured at day42 of follow-up. Treatment outcomes such as ACPR, early or late clinical failures are defined following WHO guidelines;

  day 42

Secondary Outcomes (1)

• Ex vivo susceptibility of P. vivax isolates to QN, DHA , PPQ and CQ (Mean IC50 and IC90)

  At day0 and day of recurrence of P.vivax parasitemia after initial parasite clearance assessed up to day 42

Other Outcomes (5)

• Number of patients carrying asexual parasites during 42 days follow up

  From day0 to day 42

• Number of patients with parasites carrying molecular markers of Plasmodium vivax resistance to CHL at day 0 and among recurrent vivax infections

  From day 0 to day42

• The number of patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency measured by rapid test

  day 42

Study Arms (1)

Chloroquine

OTHER

Single treatment arm

Drug: Chloroquine

Interventions

Chloroquine DRUG

efficacy of chloroquine for the treatment of Plasmodium vivax infections

Also known as: Nivaquine

Chloroquine

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Mono-infection of P. vivax by light microscopy (LM) with asexual parasite density \>250/µl
• Age ≥1year
• Axillary temperature ≥ 37.5º C and/or history of fever during the previous 48 hours;
• Patient or caregiver consent to enrolment and agree to sampling and return visits;

You may not qualify if:

• General danger signs or symptoms of severe malaria (as per WHO definitions; Annex I);
• Signs or symptoms of severe malnutrition, defined as weight-for-age ≤ 3 standard deviations below the mean (NCHS/WHO normalized reference values, Annex II);
• Slide confirmed infection with any other Plasmodium species (including mixed infections);
• Severe anaemia, defined as haemoglobin (Hb) \<7g/dl in adults and \<5g/dl in children;
• Known hypersensitivity to any of the drugs being evaluated;
• Presence of fever due to illness other than malaria;
• History of serious and/or chronic medical condition (cardiac, renal, hepatic diseases, sickle cell disease, HIV/AIDS);
• Pregnancy (confirmed by rapid test) or breastfeeding;
• Regular use of medication that may interfere with antimalarial pharmacokinetics;

Sponsors & Collaborators

• National Institute of Malariology, Parasitology and Entomology, Vietnam: lead
• Institute of Tropical Medicine, Belgium: collaborator

Study Sites (1)

Chu R Cam

Pleiku, Gia Lai, Vietnam

RECRUITING

Related Publications (8)

• Rosanas-Urgell A, Mueller D, Betuela I, Barnadas C, Iga J, Zimmerman PA, del Portillo HA, Siba P, Mueller I, Felger I. Comparison of diagnostic methods for the detection and quantification of the four sympatric Plasmodium species in field samples from Papua New Guinea. Malar J. 2010 Dec 14;9:361. doi: 10.1186/1475-2875-9-361.

  PMID: 21156052 BACKGROUND

• Koepfli C, Mueller I, Marfurt J, Goroti M, Sie A, Oa O, Genton B, Beck HP, Felger I. Evaluation of Plasmodium vivax genotyping markers for molecular monitoring in clinical trials. J Infect Dis. 2009 Apr 1;199(7):1074-80. doi: 10.1086/597303.

  PMID: 19275476 BACKGROUND

• Wampfler R, Mwingira F, Javati S, Robinson L, Betuela I, Siba P, Beck HP, Mueller I, Felger I. Strategies for detection of Plasmodium species gametocytes. PLoS One. 2013 Sep 27;8(9):e76316. doi: 10.1371/journal.pone.0076316. eCollection 2013.

  PMID: 24312682 BACKGROUND

• Auburn S, Marfurt J, Maslen G, Campino S, Ruano Rubio V, Manske M, Machunter B, Kenangalem E, Noviyanti R, Trianty L, Sebayang B, Wirjanata G, Sriprawat K, Alcock D, Macinnis B, Miotto O, Clark TG, Russell B, Anstey NM, Nosten F, Kwiatkowski DP, Price RN. Effective preparation of Plasmodium vivax field isolates for high-throughput whole genome sequencing. PLoS One. 2013;8(1):e53160. doi: 10.1371/journal.pone.0053160. Epub 2013 Jan 4.

  PMID: 23308154 BACKGROUND

• Kerlin DH, Boyce K, Marfurt J, Simpson JA, Kenangalem E, Cheng Q, Price RN, Gatton ML. An analytical method for assessing stage-specific drug activity in Plasmodium vivax malaria: implications for ex vivo drug susceptibility testing. PLoS Negl Trop Dis. 2012;6(8):e1772. doi: 10.1371/journal.pntd.0001772. Epub 2012 Aug 7.

  PMID: 22880143 BACKGROUND

• Borlon C, Russell B, Sriprawat K, Suwanarusk R, Erhart A, Renia L, Nosten F, D'Alessandro U. Cryopreserved Plasmodium vivax and cord blood reticulocytes can be used for invasion and short term culture. Int J Parasitol. 2012 Feb;42(2):155-60. doi: 10.1016/j.ijpara.2011.10.011. Epub 2011 Dec 27.

  PMID: 22240310 BACKGROUND

• Kim S, Nguon C, Guillard B, Duong S, Chy S, Sum S, Nhem S, Bouchier C, Tichit M, Christophel E, Taylor WR, Baird JK, Menard D. Performance of the CareStart G6PD deficiency screening test, a point-of-care diagnostic for primaquine therapy screening. PLoS One. 2011;6(12):e28357. doi: 10.1371/journal.pone.0028357. Epub 2011 Dec 2.

  PMID: 22164279 BACKGROUND

• Rovira-Vallbona E, Van Hong N, Kattenberg JH, Huan RM, Binh NTH, Ngoc NTH, Guetens P, Hieu NL, Hien NTT, Sang VT, Long ND, Sauve E, Duong TT, Xa NX, Erhart A, Rosanas-Urgell A. High Proportion of Genome-Wide Homology and Increased Pretreatment pvcrt Levels in Plasmodium vivax Late Recurrences: a Chloroquine Therapeutic Efficacy Study. Antimicrob Agents Chemother. 2021 Jul 16;65(8):e0009521. doi: 10.1128/AAC.00095-21. Epub 2021 Jul 16.

  PMID: 34031050 DERIVED

MeSH Terms

Conditions

Malaria, Vivax; Recurrence

Interventions

Chloroquine

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Duong Tran, MD, PhD

  National Institute of Malariology Parasitology Entomology, Hanoi, Vietnam

  PRINCIPAL INVESTIGATOR

• Anna Rosanas-Urgell, MD, PhD

  Institute of Tropical Medicine, Antwerp, Belgium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Phuc Bui, PhD, MD

CONTACT

+84 913522874; phucnimpe@yahoo.com

Duong Tran, PhD, MD

CONTACT

+8416895919; tranthanhduong@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2015
• First Posted: November 20, 2015
• Study Start: March 1, 2015
• Primary Completion: October 1, 2016
• Study Completion: December 1, 2016
• Last Updated: March 23, 2016

Record last verified: 2015-10

Locations

VN (1)