Kilimanjaro IPTi Drug Options Trial - Full Text View

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:

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.
Determination of whether a short acting antimalarial drug (Lapdap) is as effective as a long acting drug (mefloquine) when used for IPTi.
Investigation of the effect of the intensity of transmission on the requirements for a long or short acting drug for IPTi.
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:

MedlinePlus related topics: Anemia Fever Malaria

Drug Information available for: Pyrimethamine Dapsone Mefloquine hydrochloride

U.S. FDA Resources

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

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):

Cairns M, Gosling R, Carneiro I, Gesase S, Mosha JF, Hashim R, Kaur H, Lemnge M, Mosha FW, Greenwood B, Chandramohan D. Duration of protection against clinical malaria provided by three regimens of intermittent preventive treatment in Tanzanian infants. PLoS One. 2010 Mar 1;5(3):e9467.

Gosling RD, Gesase S, Mosha JF, Carneiro I, Hashim R, Lemnge M, Mosha FW, Greenwood B, Chandramohan D. Protective efficacy and safety of three antimalarial regimens for intermittent preventive treatment for malaria in infants: a randomised, double-blind, placebo-controlled trial. Lancet. 2009 Oct 31;374(9700):1521-32. Epub 2009 Sep 16.

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
Sulfadoxine-pyrimethamine
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 May 19, 2013