Kilimanjaro IPTi Drug Options Trial

This study has been completed.
Sponsor:
Collaborators:
University of Copenhagen
National Institute for Medical Research, Tanzania
Kilimanjaro Christian Medical Centre, Tanzania
Information provided by:
Gates Malaria Partnership
ClinicalTrials.gov Identifier:
NCT00158574
First received: September 8, 2005
Last updated: March 5, 2009
Last verified: March 2009
  Purpose

Malaria and anaemia are major causes of morbidity and mortality in children in sub-Saharan Africa. Administration of three courses of sulfadoxine/pyrimethamine (SP) as intermittent preventive treatment (IPTi) to infants when they receive EPI vaccines reduced the incidence of malaria and anaemia in infants in an area with low SP resistance, low transmission pressure and high bednet use. However, it is not clear whether this observation can be generalised to areas with high transmission and high SP resistance. The mechanism of the protective effect of IPTi is unclear. There is an urgent need to identify other anti-malarial drugs that could be used for IPTi instead of SP.

This study objectives are:

  1. Identification of a drug that could be used safely and effectively for IPTi instead of SP in areas, such as north eastern Tanzania, where there is a high level of resistance to SP and amodiaquine.
  2. Determination of whether a short acting antimalarial drug (Lapdap) is as effective as a long acting drug (mefloquine) when used for IPTi.
  3. Investigation of the effect of the intensity of transmission on the requirements for a long or short acting drug for IPTi.
  4. Assessment of the effect of IPTi on the development of clinical immunity in children in low and high transmission areas.

A randomised trial with four treatment regimes is proposed which will be conducted in two different transmission settings. The four treatment regimens are as follows: (1) placebo; (2) mefloquine; (3) Lapdap; (4) SP. All medications will be given at the time of immunisation with DPT/polio 2, DPT/polio 3, and measles vaccines. The study will involve 1280 infants in a high endemic area and 2440 infants in a low endemic area, in Tanzania.The primary outcome is the incidence of clinical malaria.


Condition Intervention Phase
Malaria
Drug: sulphadoxine-pyrimethamine
Drug: mefloquine
Drug: Chlorproguanil-dapsone
Drug: Placebo
Drug: Sulphadoxine-pryrimethamine
Drug: IPTi mefloquine
Drug: Chlorproguanil dapsone
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: Drug Options for Intermittent Preventive Treatment for Malaria in Infants in an Area With High Resistance to Sulfadoxine/Pyrimethamine: an Evaluation of Short and Long-Acting Antimalarial Drugs

Resource links provided by NLM:


Further study details as provided by Gates Malaria Partnership:

Primary Outcome Measures:
  • 1. Incidence of clinical malaria: [(history of fever during previous 2 days or axillary temperature >37.5ºC) + parasitaemia of any density + absence of any other obvious causes of fever] during the period of 3-11 months of age [ Time Frame: 3-11 months of age ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 1.Mean Hb at 10-12 months of age (one month after the third course of IPTi) [ Time Frame: 10-12 months of age ] [ Designated as safety issue: No ]
  • 2.Incidence of severe anaemia (Hb <7 g/dl) during the period of 3-11 months of age [ Time Frame: 3-11 months of age ] [ Designated as safety issue: No ]
  • 3.Prevalence of parasitaemia at 10-12 months of age (one month after the third course of IPTi) [ Time Frame: 10-12 months of age ] [ Designated as safety issue: No ]
  • 4.Incidence of clinical malaria [as defined above] during the period of 12-23 months of age. [ Time Frame: 12-23 months of age ] [ Designated as safety issue: No ]
  • 5.Level and repertoires of plasma antibodies to Plasmodium falciparum variant surface antigen (anti-VSA antibodies) at 10 and 18 months of age. [ Time Frame: 10 and 18 months of age ] [ Designated as safety issue: No ]

Enrollment: 2419
Study Start Date: January 2005
Study Completion Date: June 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
IPTi placebo
Drug: Placebo
Placebo
Experimental: Sulphadoxine-pyrimethamine
IPTi SP
Drug: sulphadoxine-pyrimethamine
Other Name: Fansidar
Drug: Sulphadoxine-pryrimethamine
IPTi doses 1 and 2, at ages 2 and 3 months, sulphadoxine 250mg, pyrimethamine 12.5mg IPTi doses 3, at 9 months of age, sulphadoxine 500mg, pyrimethamine 25mg
Other Name: Fansidar
Experimental: Mefloquine Drug: mefloquine
Other Name: Larium
Drug: IPTi mefloquine
IPTi doses 1 & 2 at ages 2 & 3 months, mefloquine 125mg IPTi dose 3 at 9 months, mefloquine 250mg
Other Name: Larium
Experimental: Chlorproguanil dapsone Drug: Chlorproguanil-dapsone
Other Name: Lapdap
Drug: Chlorproguanil dapsone
IPTi doses 1 and 2 at ages 2 and 3 months, doses 15mg chlorproguanil and 18.75mg dapsone IPTi dose 3 at 9 months of age, doses 22.5mg chlorproguanil and 28.13mg dapsone
Other Name: Lapdap

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   2 Months to 24 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • All infants attending EPI clinics at the 12 study health facilities for first vaccinations. Infants who live within the catchment area of the study health facility and are less than 3 months of age at the time of DPT and Polio 1 vaccination will be eligible for inclusion in the study.

Exclusion Criteria:

  • Infants having any of the following conditions will be excluded: (1) history of allergy to study drugs; (2) history of convulsions; (3) clinical features of severe malnutrition or chronic illness including infants with signs of AIDS [HIV prevalence in women of reproductive age in the study area was 11.5% in 1999]39 (4) plans to leave the study area before 12 months of age.(5) weighs <4.5 kgs (6) caretaker declines to give consent.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00158574

Locations
Tanzania
Ministry of Health, Korogwe and Same District MCH clinics
Tanga, Tanga and Kilimanjaro, Tanzania
Sponsors and Collaborators
Gates Malaria Partnership
University of Copenhagen
National Institute for Medical Research, Tanzania
Kilimanjaro Christian Medical Centre, Tanzania
Investigators
Study Director: Roly Gosling, MBChB, MRCP London School of Hygiene and Tropical Medicine
Principal Investigator: Daniel Chandramohan, MBBS,PhD London School of Hygiene and Tropical Medicine
Principal Investigator: Brian Greenwood, FRCP, FRS London School of Hygiene and Tropical Medicine
  More Information

No publications provided by Gates Malaria Partnership

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Daniel Chandramohan, London School of Hygiene & Tropical Medicine
ClinicalTrials.gov Identifier: NCT00158574     History of Changes
Other Study ID Numbers: ITDCVF01
Study First Received: September 8, 2005
Last Updated: March 5, 2009
Health Authority: Tanzania: Ministry of Health

Keywords provided by Gates Malaria Partnership:
intermittent preventive treatment
malaria
efficacy
safety
drug options

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases
Antimalarials
Dapsone
Mefloquine
Pyrimethamine
Sulfadoxine
Chlorproguanil
Proguanil
Fanasil, pyrimethamine drug combination
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 August 01, 2014