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Dihydroartemisinin (DHA)-Piperaquine for IPT to Prevent Malaria in Children in Burkina Faso

This study has been completed.
Sponsor:
Collaborator:
BEIJING HOLLEY-COTEC PHARMACEUTICALS CO. LTD.
Information provided by:
London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier:
NCT00941785
First received: June 18, 2009
Last updated: March 18, 2011
Last verified: March 2011
  Purpose

The aim of the study is to determine whether piperaquine plus dihydroartemisinin (DHA-PQ) is as effective, and better tolerated, than sulfadoxine-pyrimethamine plus amodiaquine (SP+AQ), when used for seasonal Intermittent Preventive Treatment (IPT) to prevent malaria in children aged 3 to 59 months in Bobo-Dioulasso, Burkina Faso and to determine the pharmacokinetics of piperaquine in children.


Condition Intervention Phase
Malaria
Drug: DHA-PQ
Drug: SP-AQ
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Randomized Trial of the Efficacy, Safety, Tolerability and Pharmacokinetics of Dihydroartemisinin-piperaquine for Seasonal IPT to Prevent Malaria in Children Under 5 Years

Resource links provided by NLM:


Further study details as provided by London School of Hygiene and Tropical Medicine:

Primary Outcome Measures:
  • Efficacy against clinical malaria [ Time Frame: August to December 2009 ] [ Designated as safety issue: No ]
  • Incidence of adverse events [ Time Frame: Within 7 days of each treatment round and within 1 month of treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics of piperaquie: the oral clearance (CL/F), AUC, steady state volume of distribution(s) (Vss/F), inter-compartment clearance(s) (Q/F) and absorption rate (ka) will be estimated. [ Time Frame: during 30 days after start of treatment ] [ Designated as safety issue: No ]

Enrollment: 1500
Study Start Date: July 2009
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DHA-PQ
Three monthly administrations of dihydroartemisinin (DHA) plus piperaquine (PQ) in August, September and October.
Drug: DHA-PQ

Three monthly administrations of Duocotexcin (DHA-PQ):

dihydroartemisinin 2.1mg/kg and piperaquine phosphate 16.8 mg/kg once daily for three days

Other Name: Seasonal IPTc with Duocotexcin (Holley)
Active Comparator: SP-AQ
Three monthly administrations of sulfadoxine-pyrimethamine plus amodiaquine
Drug: SP-AQ

Three monthly administrations of sulfadoxine-pyrimethamine plus amodiaquine:

One dose of Sulfadoxine 25mg/kg and pyrimethamine 1.25mg/kg Three daily doses of amodiaquine phosphate 10mg/kg

Other Name: Seasonal IPTc with Fansidar plus amodiaquine (Flavoquine)

Detailed Description:

There is evidence from several studies that in areas where the transmission of malaria is seasonal, the use of IPT can reduce substantially the incidence of clinical malaria in children under the age of five years, by as much as 90% (Greenwood et al, Trends in Parasitology 24(11):485-6, 2008). The most effective regimen is SP+AQ but alternative regimens are needed because amodiaquine can be poorly tolerated (Sokhna et al PlosOne 3:e1471, 2008) and resistance to SP is increasing. In recent trials in Senegal and The Gambia, PQ combined with DHA or SP was as effective against malaria, and better tolerated, than SP+AQ. Of these regimens, only DHA+PQ is licensed for use as an antimalarial in African countries. However there are no data on pharmacokinetics of PQ when used for IPT in children, and the impact of DHA+PQ in preventing spread of resistance is not known. This trial aims to provide this information in order to evaluate the suitability of DHA+PQ for use for seasonal IPT in children and to determine the optimum dose regimen for piperaquine.

Malaria (caused primarily by Plasmodium falciparum) is endemic in the southern third of Burkina Faso, occurring seasonally between June to November, with most cases occurring between August and October. In Burkina Faso there has been no evidence of a recent decline in malaria incidence as seen in some other African countries. Although the policy is to treat uncomplicated malaria with artemisin combinations, in practice chloroquine remains the treatment used in most health facilities. Several studies have shown that seasonal IPT in children (IPTc) can provide a high degree of protection against clinical malaria. SP+AQ is the most effective regimen but amodiaquine is not well tolerated and resistance to SP is increasing n many areas. Alternative regimens are required. Piperaquine (PQ), a long acting antimalarial used for prophylaxis in China, is suitable for use for IPT. In studies in Senegal and The Gambia piperaquine plus SP or dihydroartemisinin (DHA) was as effective and better tolerated than SP+AQ. The purpose of this study is to determine whether DHA-PQ is more effective than SP+AQ in preventing spread of drug resistant parasite genotypes and to determine the pharmacokinetics of piperaquine in children who receive this drug for IPT. Little was known about the pharmacokinetics of piperaquine until recently, and there is currently only limited information about the pharmacokinetics of piperaquine in children. The pharmacokinetic data from this study will allow us to estimate the optimum dose regimen for piperaquine; the current recommended regimen for DHA-PQ is three doses over three days. For IPT, a single dose regimen is highly desirable as it would be easier to deliver and better accepted by communities.

1500 children aged 3 to 59 months will be enrolled and randomized to receive 3 monthly administrations of DHA-PQ or SP-AQ, in August, September and October. From August to November children will be visited twice weekly to check for malaria symptoms.

A subset of 45 children in each treatment group will be asked to provide a venous blood sample on days 0 and 7 for analysis of biochemical and haematological parameters.

In the DHA-PQ group only, a subset of 210 children will be asked to provide finger prick blood samples for PK analysis on day 0, between day 0 and day 6, on day 7, and between day 8 and day 30. To calibrate measurements of drug concentration in peripheral blood against existing PK models, each month 17 of these children will be asked to also provide a venous sample (up to 2ml taken into a vacutainer) on three occasions (one between day 0 and 6, one on day 7, and one between day 8 and 30). In addition, a separate group of 750 children aged 3 to 59 months will be recruited to be surveyed at the end of the transmission season to determine the prevalence of malaria parasitaemia and of drug-resistance parasite genotypes in the study area.

  Eligibility

Ages Eligible for Study:   3 Months to 59 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • signed consent from a parent
  • age 3-59 months at enrolment
  • no history of allergy to study drugs
  • no chronic illness

Exclusion Criteria:

  • history of allergy to study drugs
  • intention to move away from the study area before the end of 2009
  • any chronic illness
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00941785

Locations
Burkina Faso
IRSS
Bobo-Dioulasso, Burkina Faso, BP545
Sponsors and Collaborators
London School of Hygiene and Tropical Medicine
BEIJING HOLLEY-COTEC PHARMACEUTICALS CO. LTD.
Investigators
Study Director: Jean-Bosco Ouédraogo, MD IRSS, Direction Régionale,BP 545 Bobo-Dioulasso (Burkina Faso)
Study Chair: Paul JM Milligan, PhD London School of Hygiene and Tropical Medicine
Principal Investigator: Issaka Zongo, MD IRSS, Burkina Faso and LSHTM, UK
  More Information

No publications provided by London School of Hygiene and Tropical Medicine

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr Issaka Zongo, IRSS, BP 545 Bobo-Dioulasso (Burkina Faso)
ClinicalTrials.gov Identifier: NCT00941785     History of Changes
Other Study ID Numbers: EC5550
Study First Received: June 18, 2009
Last Updated: March 18, 2011
Health Authority: Burkina Faso: Direction Generale de la Pharmacie du Medicament et des Laboratoires

Keywords provided by London School of Hygiene and Tropical Medicine:
Malaria
Intermittent Preventive Treatment
IPTc
sIPTc
Burkina Faso

Additional relevant MeSH terms:
Malaria
Parasitic Diseases
Protozoan Infections
Amodiaquine
Artemisinins
Dihydroartemisinin
Fanasil, pyrimethamine drug combination
Piperaquine
Anti-Infective Agents
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014