Clinical trial NCT00206739: Intermittent Treatment With Sulfadoxine-pyrimethamine for Malaria Control in Infants
Official title: Intermittent Treatment With Sulfadoxine-pyrimethamine for Malaria Control in Infant: a Randomized, Double-blind, and Placebo-controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Malaria
Anemia
Keywords: Malaria
Anemia
IPTi
Intermittent Preventive Treatment in Infants
Sulfadoxine-Pyrimethamine
Chemoprophylaxis
Ghana
Lead sponsor: Bernhard Nocht Institute for Tropical Medicine
Sponsor class: OTHER_GOV
Collaborators: name: German Federal Ministry of Education and Research
name: Deutscher Akademischer Austausch Dienst
name: The Volkswagen Foundation
First posted: 2005-09-21
Enrollment: 1070
Sex: ALL
Minimum age (years): 2
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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

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

Eligibility criteria: 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

Primary outcomes:
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)
measure: • Determination of the rate of clinical malaria and anemia after suspending an extended intermittent treatment for analysis of possible rebound effects
measure: • Evaluation of safety and adverse effects of the administration of single doses of sulfadoxine-pyrimethamine in infants and children
Secondary outcomes:
measure: • Rate and time points of hospitalizations with anemia, malaria or other diseases
measure: • Rate and time points of severe anemia episodes
measure: • Proportion and rates of children with one or more episodes of malaria or anemia in the age of 3 to 12 months of life
measure: • Antibody responses against parasite antigens
measure: • Multiplicity of P. falciparum infections
measure: • Proportion of P. falciparum isolates with SP resistance
measure: • Influence of host genetic variants on the rate of P. falciparum infections
Other outcomes:
Locations:
city: Kumasi
country: Ghana
facility: Kumasi Centre for Collaborative Research in Tropical Medicine
state: Ashanti Region
Study officials:
affiliation: Kumasi Centre for Collaborative Research in Tropical Medicine
name: Ohene Adjei, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Bernhard Nocht Institute for Tropical Medicine Hamburg, Infection Epidemiology
name: Jürgen May, PD Dr.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.