Intermittent Treatment With Sulfadoxine-pyrimethamine for Malaria Control in Infants

Intermittent Treatment With Sulfadoxine-pyrimethamine for Malaria Control in Infant: a Randomized, Double-blind, and Placebo-controlled Clinical Trial

The purpose of this study is to assess the effectiveness of Intermittent Preventive Treatment in Infants (IPTi) with Sulfadoxine-Pyrimethamine to reduce the numbers of malaria attacks, episodes of anemia, and the overall morbidity and mortality

Study Overview

• Status: Completed
• Conditions: Anemia; Malaria
• Intervention / Treatment: Drug: Sulfadoxine (12.5 mg)/Pyrimethamine (250 mg)

Detailed Description

In order to define the effectiveness of Intermittent Preventive Treatment in Infants (IPTi) with Sulfadoxine-Pyrimethamine, a novel principle of malaria intervention, the following parameters are evaluated: i) the level of protection from malaria attacks and episodes of anemia during the treatment period, ii) the level of protection from severe malaria during the treatment period, iii) the effect on malaria morbidity after sustaining treatment, iv) the decrease of overall morbidity and mortality, including the number of hospital admissions and visits of hospital outpatient departments v) the influence of the intervention on the development of drug resistances, vi) the impact of the intervention on the development of immunity, vii) the possible influence of the intervention on sub-clinical organ dysfunction due to chronic Plasmodium falciparum infection. Parts of the study are performed in collaboration with the Laboratory of Research, Hospital Albert Schweitzer, Lambaréné, Gabon and the School of Medicine and Health Sciences, University of Development Studies, Tamale, Ghana

• Study Type: Interventional
• Enrollment (Actual): 1070
• Phase: Phase 4

Contacts and Locations

Study Locations

• Ghana
  • Ashanti Region
    • Kumasi, Ashanti Region, Ghana
      • Kumasi Centre for Collaborative Research in Tropical Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 4 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Informed consent by parent/guardian (written or oral)
• Permanent residentship in the study area
• Age of 3 months +/-4 weeks

Exclusion Criteria:

• Hypersensitivity to sulfonamides or pyrimethamine (skin rashes, evidence of hemolysis including dark urine and/or purpura, presumptive signs of bone marrow depression such as sore throat and/or mouth ulcers)
• Other severe adverse events related to pyrimethamine-sulfadoxine application
• Signs of severe hepatic or renal dysfunction not due to malaria
• Other reasons after decision of the study physician

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

What is the study measuring?

Primary Outcome Measures

Outcome Measure
• Efficacy of an extended intermittent treatment with sulfadoxine-pyrimethamine for the control of clinical malaria and anemia (proportion and rates of children with one or more episodes of malaria or anemia in the age of 3 to 21 months of life)
• Determination of the rate of clinical malaria and anemia after suspending an extended intermittent treatment for analysis of possible rebound effects
• Evaluation of safety and adverse effects of the administration of single doses of sulfadoxine-pyrimethamine in infants and children

Secondary Outcome Measures

Outcome Measure
• Rate and time points of hospitalizations with anemia, malaria or other diseases
• Rate and time points of severe anemia episodes
• Proportion and rates of children with one or more episodes of malaria or anemia in the age of 3 to 12 months of life
• Antibody responses against parasite antigens
• Multiplicity of P. falciparum infections
• Proportion of P. falciparum isolates with SP resistance
• Influence of host genetic variants on the rate of P. falciparum infections

Collaborators and Investigators

• Sponsor: Bernhard Nocht Institute for Tropical Medicine
• Collaborators: German Federal Ministry of Education and Research; Deutscher Akademischer Austausch Dienst; The Volkswagen Foundation
• Investigators: Principal Investigator: Ohene Adjei, Prof. Dr., Kumasi Centre for Collaborative Research in Tropical Medicine; Study Director: Jürgen May, PD Dr., Bernhard Nocht Institute for Tropical Medicine Hamburg, Infection Epidemiology

Publications and helpful links

General Publications

• Schellenberg D, Menendez C, Kahigwa E, Aponte J, Vidal J, Tanner M, Mshinda H, Alonso P. Intermittent treatment for malaria and anaemia control at time of routine vaccinations in Tanzanian infants: a randomised, placebo-controlled trial. Lancet. 2001 May 12;357(9267):1471-7. doi: 10.1016/S0140-6736(00)04643-2.
• Menendez C, Kahigwa E, Hirt R, Vounatsou P, Aponte JJ, Font F, Acosta CJ, Schellenberg DM, Galindo CM, Kimario J, Urassa H, Brabin B, Smith TA, Kitua AY, Tanner M, Alonso PL. Randomised placebo-controlled trial of iron supplementation and malaria chemoprophylaxis for prevention of severe anaemia and malaria in Tanzanian infants. Lancet. 1997 Sep 20;350(9081):844-50. doi: 10.1016/S0140-6736(97)04229-3.
• Massaga JJ, Kitua AY, Lemnge MM, Akida JA, Malle LN, Ronn AM, Theander TG, Bygbjerg IC. Effect of intermittent treatment with amodiaquine on anaemia and malarial fevers in infants in Tanzania: a randomised placebo-controlled trial. Lancet. 2003 May 31;361(9372):1853-60. doi: 10.1016/s0140-6736(03)13504-0.
• Verhoef H, West CE, Nzyuko SM, de Vogel S, van der Valk R, Wanga MA, Kuijsten A, Veenemans J, Kok FJ. Intermittent administration of iron and sulfadoxine-pyrimethamine to control anaemia in Kenyan children: a randomised controlled trial. Lancet. 2002 Sep 21;360(9337):908-14. doi: 10.1016/S0140-6736(02)11027-0. Erratum In: Lancet 2002 Oct 19;360(9341):1256.
• May J, Adjei S, Busch W, Gabor JJ, Issifou S, Kobbe R, Kreuels B, Lell B, Schwarz NG, Adjei O, Kremsner PG, Grobusch MP. Therapeutic and prophylactic effect of intermittent preventive anti-malarial treatment in infants (IPTi) from Ghana and Gabon. Malar J. 2008 Oct 1;7:198. doi: 10.1186/1475-2875-7-198.
• Kobbe R, Adjei S, Kreuzberg C, Kreuels B, Thompson B, Thompson PA, Marks F, Busch W, Tosun M, Schreiber N, Opoku E, Adjei O, Meyer CG, May J. Malaria incidence and efficacy of intermittent preventive treatment in infants (IPTi). Malar J. 2007 Dec 9;6:163. doi: 10.1186/1475-2875-6-163.

Helpful Links

• Homepage of the Kumasi Centre for Collaborative Research (study site)

Study record dates

Study Major Dates

• Study Start: January 1, 2003
• Primary Completion (Actual): September 1, 2005
• Study Completion (Actual): September 1, 2005

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 21, 2005

Study Record Updates

• Last Update Posted (Estimate): March 30, 2010
• Last Update Submitted That Met QC Criteria: March 29, 2010
• Last Verified: September 1, 2005

More Information

Terms related to this study

• Keywords: Malaria; Anemia; IPTi; Intermittent Preventive Treatment in Infants; Sulfadoxine-Pyrimethamine; Chemoprophylaxis; Ghana
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Folic Acid Antagonists; Anti-Infective Agents, Urinary; Renal Agents; Pyrimethamine; Sulfadoxine
• Other Study ID Numbers: 01KA0202-K7.3; 01KA0202

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No