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

NCT00361114 | Terminated Phase 3 DMC

• 1 other identifier: DIF 35
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Malaria

Outcome Measures

Primary Outcomes (13)

• Clinical /Parasitological Outcomes (WHO 2003)

  Day 14 and 28

• Early Treatment Failure (ETF)

  3 days

• § Development of danger signs or severe malaria on Day 1, 2, or 3, in the presence of parasitemia

  3 Days

• § Parasitemia on Day 2 higher than Day 0 count irrespective of axillary temperature

  2 nd day

• § Parasitemia on Day 3 with axillary temperature ≥37.5°C

  3 rd day

• § Parasitemia on Day 3 ≥ 25% of count on Day 0

  3 rd Day

• Late Clinical Failure (LCF)

  After Day 3 to day 28

• § 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

  Day 4 - 28

• § 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

  Day 4 to Day 28

• Late parasitological failure (LPF) -

  Day 4 - 28

• 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)

  Day 14, 21, or 28

• Adequate Clinical and Parasitological Response (ACPR) -

  Day 28

• Absence of parasitemia on Day 28 irrespective of axillary temperature, without previously meeting any of the criteria of ETF, LCF or LPF

  Day 28

Study Arms (3)

A

ACTIVE COMPARATOR

SP in symptomatic children aged 6-59 months

Drug: sulphadoxine/pyrimethamine

B

EXPERIMENTAL

SP to asymptomatic infected children aged 2-10 months

Drug: Sulfadoxine/pyrimethamine

C

EXPERIMENTAL

Chlorproguanil/dapsone in symptomatic 6-59 month old children

Drug: Chlorproguanil/dapsone

Interventions

sulphadoxine/pyrimethamine DRUG

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)

Also known as: Fansidar

A

Chlorproguanil/dapsone DRUG

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).

Also known as: Lapdap

C

Sulfadoxine/pyrimethamine DRUG

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)

Also known as: Fansidar

B

Eligibility Criteria

• Age: 2 Months - 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead

Study Sites (1)

Hale Dispensary

Korogwe, Tanga, Tanzania

Location

Related Publications (1)

• Gesase S, Gosling RD, Hashim R, Ord R, Naidoo I, Madebe R, Mosha JF, Joho A, Mandia V, Mrema H, Mapunda E, Savael Z, Lemnge M, Mosha FW, Greenwood B, Roper C, Chandramohan D. High resistance of Plasmodium falciparum to sulphadoxine/pyrimethamine in northern Tanzania and the emergence of dhps resistance mutation at Codon 581. PLoS One. 2009;4(2):e4569. doi: 10.1371/journal.pone.0004569. Epub 2009 Feb 24.

  PMID: 19238219 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

fanasil, pyrimethamine drug combination; chloroguanil, dapsone drug combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 3, 2006
• First Posted: August 7, 2006
• Study Start: July 1, 2006
• Primary Completion: August 1, 2007
• Study Completion: October 1, 2007
• Last Updated: January 26, 2017

Record last verified: 2017-01

Locations

TA (1)