IPT and Efficacy of Sulphadoxine/Pyrimethamine and Chlorproguanil/Dapsone in 6-59 Month Old Children With Malaria.

This study has been terminated.
(SP arms were stopped due to high levels of treatment failure.CD not available.)
Sponsor:
Information provided by:
Gates Malaria Partnership
ClinicalTrials.gov Identifier:
NCT00361114
First received: August 3, 2006
Last updated: May 1, 2008
Last verified: May 2008
  Purpose

Intermittent Preventive Treatment of malaria in infants is a promising strategy to reduce incidence of clinical malaria in children under the age of 1 year. It is likely to be implemented as a malaria control strategy in Tanzania using sulfadoxine/pyremethamine SP. SP is failing as a first line treatment for clinical episodes of malaria and government policy is driving a change to use Artemesin Combination Therapy (ACT). The main ongoing Kilimanjaro IPTi study is looking at alternatives to SP for use in IPTi. Currently, as there is no evidence for the use of other drugs for IPT, SP will be continued for IPT in pregnancy and in infants. This study proposes to measure the efficacy of SP and chlorproguanil/dapsone (CD), in symptomatic 6- 59 month old children using standard methodology. These are both study drugs in the main IPTi study. This will help us to see how the efficacies of SP and CD in sick children relate to the efficacies for treating asymptomatic children with IPTi. In addition this proposal aims to test the efficacy of SP given to 2-10 month old asymptomatic infants (the target group for IPTi). Evidence suggests that asymptomatic malaria infections with low parasitaemia have a higher cure rate than symptomatic infections with high parasitaemia even when markers of resistance are highly prevalent. This second study aims to quantify this difference and will produce evidence to help policy makers know when drugs used for IPTi should be changed. Both studies will be open label and run concurrently in Hale, Korogwe district near to the main Kilimanjaro IPTi site in Tanzania.


Condition Intervention Phase
Malaria
Drug: sulphadoxine/pyrimethamine
Drug: Chlorproguanil/dapsone
Drug: Sulfadoxine/pyrimethamine
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy of Sulphadoxine/Pyrimethamine and Chlorproguanil/Dapsone in 6-59 Month Old Children With Uncomplicated Malaria and in 2-10 Month Old Asymptomatic Infants.

Resource links provided by NLM:


Further study details as provided by Gates Malaria Partnership:

Primary Outcome Measures:
  • Clinical /Parasitological Outcomes (WHO 2003) [ Time Frame: Day 14 and 28 ] [ Designated as safety issue: No ]
  • Early Treatment Failure (ETF) [ Time Frame: 3 days ] [ Designated as safety issue: No ]
  • § Development of danger signs or severe malaria on Day 1, 2, or 3, in the presence of parasitemia [ Time Frame: 3 Days ] [ Designated as safety issue: No ]
  • § Parasitemia on Day 2 higher than Day 0 count irrespective of axillary temperature [ Time Frame: 2 nd day ] [ Designated as safety issue: No ]
  • § Parasitemia on Day 3 with axillary temperature ≥37.5°C [ Time Frame: 3 rd day ] [ Designated as safety issue: No ]
  • § Parasitemia on Day 3 ≥ 25% of count on Day 0 [ Time Frame: 3 rd Day ] [ Designated as safety issue: No ]
  • Late Clinical Failure (LCF) [ Time Frame: After Day 3 to day 28 ] [ Designated as safety issue: No ]
  • § Development of danger signs or severe malaria from Day 4 to Day 28 in the presence of parasitemia, without previously meeting any of the criteria of ETF [ Time Frame: Day 4 - 28 ] [ Designated as safety issue: No ]
  • § Presence of parasitemia and axillary temperature ≥37.5° C on any day from Day 4 to Day 28, without previously meeting any of the criteria of ETF [ Time Frame: Day 4 to Day 28 ] [ Designated as safety issue: No ]
  • Late parasitological failure (LPF) - [ Time Frame: Day 4 - 28 ] [ Designated as safety issue: No ]
  • Presence of parasitemia on Day 14, 21, or 28 and axillary temperature <37.5°C without previously meeting any of the criteria of ETF or LCF (after exclusion of re-infection by PCR for failures at days 14-28) [ Time Frame: Day 14, 21, or 28 ] [ Designated as safety issue: No ]
  • Adequate Clinical and Parasitological Response (ACPR) - [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • Absence of parasitemia on Day 28 irrespective of axillary temperature, without previously meeting any of the criteria of ETF, LCF or LPF [ Time Frame: Day 28 ] [ Designated as safety issue: No ]

Enrollment: 112
Study Start Date: July 2006
Study Completion Date: October 2007
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A
SP in symptomatic children aged 6-59 months
Drug: sulphadoxine/pyrimethamine
Sulfadoxine/pyremethamine (SP) given as a single dose per manufacturers recommendation (tablets 500mg sulphadoxine and 15mg pyremethamine; child's body weight 5-10Kgs ½ tablet, 11-20Kgs 1 tablet, 21-30 Kgs 1 ½ tablets)
Other Name: Fansidar
Experimental: B
SP to asymptomatic infected children aged 2-10 months
Drug: Sulfadoxine/pyrimethamine
Sulfadoxine/pyremethamine (SP) given as a single dose per manufacturers recommendation (tablets 500mg sulphadoxine and 15mg pyremethamine; child's body weight 5-10Kgs ½ tablet, 11-20Kgs 1 tablet, 21-30 Kgs 1 ½ tablets)
Other Name: Fansidar
Experimental: C
Chlorproguanil/dapsone in symptomatic 6-59 month old children
Drug: Chlorproguanil/dapsone
Chlorproguanil/ dapsone (CD) given daily for 3 days per manufacturers recommendations (tablets chlorproguanil 15mg/ dapsone 18.75 mg; 5-7.9Kgs 1 tablet, 8-11.9 Kg 1 ½ tablets, 12-15.9 2 tablets, 16-20.9 Kgs 2 ½ tablets, 21- 40Kg 5 tablets).
Other Name: Lapdap

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   2 Months to 59 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

For 6-59 month study

Inclusion Criteria:

  • Aged 6-59 months
  • Weight of 4.5 Kgs or greater.
  • Not enrolled in IPTi trial
  • Absence of severe malnutrition (defined as a child whose weight-for-height is below 3 standard deviations of less than 70% of the median of WHO reference values, or who has symmetrical edema involving at least the feet)
  • A slide-confirmed infection with P. falciparum only
  • Initial parasite density between 2,000 and 200,000 asexual parasites per microliter.
  • Absence of general danger signs among children < 5 years (see below) Measured axillary temperature ³37.5 °C
  • Ability to attend stipulated follow-up visits
  • Informed consent provided by parent/guardian
  • Absence of history of hypersensitivity reactions to any of the drugs being evaluated

Exclusion Criteria:

  • Enrolled in IPTi trial
  • Severe malnutrition (defined as above)
  • No slide confirmed infection with P. falciparum
  • Initial parasite density < 2,000 or > 200,000 asexual parasites per microliter.
  • Presence of general danger signs among children < 5 years (inability to drink or breastfeed; vomiting everything; recent history of convulsions; lethargy or unconsciousness; inability to sit or stand up) or other signs of severe and complicated falciparum malaria according to WHO definitions
  • Measured axillary temperature <37.5 °C
  • Inability to attend stipulated follow-up visits
  • Informed consent not provided by parent/guardian
  • History of hypersensitivity reactions to any of the drugs being evaluated

For 2-10 month study

Inclusion criteria.

  • Aged 2-10 months
  • Weight of 4.5 Kgs or greater.
  • Not enrolled in IPTi trial
  • Absence of severe malnutrition
  • A slide-confirmed infection with P. falciparum only
  • Any parasite density assessed by research microscopists.
  • Absence of general danger signs among children < 5 years (inability to drink or breastfeed; vomiting everything; recent history of convulsions; lethargy or unconsciousness; inability to sit or stand up) or other signs of severe and complicated falciparum malaria according to WHO definitions
  • Measured axillary temperature < 37.5 °C
  • Ability to attend stipulated follow-up visits
  • Informed consent provided by parent/guardian
  • Absence of history of hypersensitivity reactions to SP.

Exclusion criteria are not listed separately in the WHO protocol, as they are the opposite of the inclusion criteria.

  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: NCT00361114

Locations
Tanzania
Hale Dispensary
Korogwe, Tanga Region, Tanzania
Sponsors and Collaborators
Gates Malaria Partnership
Investigators
Principal Investigator: Roly D Gosling, MD London School of Hygiene and Tropical Medicine
Principal Investigator: Samwel Gesase, MD National Institute of Medical Research, Tanzania
Principal Investigator: Jaqueline Mosha, MD Kilimanjaro Christian Medical College, Tanzania
  More Information

No publications provided by Gates Malaria Partnership

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr Roly Gosling, PI Drug Resistance Working Group,, IPTi Consortium
ClinicalTrials.gov Identifier: NCT00361114     History of Changes
Other Study ID Numbers: DIF 35
Study First Received: August 3, 2006
Last Updated: May 1, 2008
Health Authority: Tanzania: National Institute for Medical Research

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases
Dapsone
Pyrimethamine
Sulfadoxine
Chlorproguanil
Proguanil
Sulfadoxine-pyrimethamine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents, Urinary
Renal Agents
Antimetabolites

ClinicalTrials.gov processed this record on July 26, 2014