Clinical trial NCT01722539: Impact IPT With Sulfadoxine-pyrimethamine or Sulfadoxine-pyrimethamine Plus Piperaquine in Schoolchildren
Official title: Efficacy and Safety of Sulfadoxine-pyrimethamine or Sulfadoxine-pyrimethamine Plus Piperaquine Regimens Delivered Through Intermittent Preventive Treatment in Schoolchildren of Democratic Republic of Congo: A Randomised Control Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Healthy
Keywords: intermittent
preventive
treatment
malaria
soil transmitted helminths
schistosomiasis
schoolchildren
Lead sponsor: Universiteit Antwerpen
Sponsor class: OTHER
Collaborators: name: Fund for Scientific Research, Flanders, Belgium
name: University of Kinshasa
First posted: 2012-11-07
Enrollment: 616
Sex: ALL
Minimum age (years): 5
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Considering the facts that: (i) IPT of malaria provides substantial protection against anaemia and malaria in school children (ii); SP resistance has no significant impact on the prophylactic efficacy (iii) SP-PQ is safe and as efficacious as SP: the investigators hypothesize that antimalarial IPT with SP and SP-PQ will improve haemoglobin concentration, reduce anaemia prevalence, malaria incidence and parasitaemia, and improve malnutrition and school performance in school-aged children of Congo.

Detailed description: STUDY RATIONAL The education sector represents a reliable system for malaria control. Intermittent preventive therapy in schoolchildren (IPTsc) is likely the most feasible and appropriate chemoprevention in stable and endemic areas because schoolchildren are usually asymptomatic to malaria infection and are consequently untreated in practice. Therefore, if proven effective, IPTsc would be of direct benefit for the schoolchild, contribute to malaria control at school, and facilitate community-wide the implementation of other control interventions i.e. vector control, Intermittent preventive therapy in infants (IPTi), and prompt diagnosis and treatment (PDT). Nevertheless, evidence about use of IPTsc is not yet substantiated as only two clinical studies have so far been performed on IPTsc in hyper endemic areas. Further clinical trials are warranted in other settings. Through a randomised controlled trial (RCT) we will assess the efficacy and safety, of two IPT regimens versus controls in school children of the DRCongo.

STUDY DRUGS Favourable drugs for use as IPT should balance long half-life against efficacy, safety, tolerability and potentiality for cross-resistance selection.(16) Use of long-acting drugs would result in fewer intake and higher treatment compliance. Sulfadoxine-pyrimethamine is an established used product in the indication of IPT in pregnancy. The drug has further proven safety and tolerability in children in clinical trials. SP is slowly eliminated and allows 60 days antimalaria protection for fully sensitive P. falciparum. Other long-acting drugs available are mefloquine, amodiaquine, and piperaquine. However, due safety concern mefloquine might not be optimal for IPT. Amodiaquine is not suitable for IPT due to its 3 days treatment regimen that may be a concern regarding compliance. Piperaquine has been extensively used for mass prophylaxis and treatment since 1978 in China and other malaria endemic countries of Asia.(20) Piperaquine has a long half-live and points as good IPT candidate in endemic country with SP resistance. For this study sulfadoxine-pyrimethamine combined with piperaquine (SP-PQ) plus will be used. SP and SP-PQ will be given at 4 months intervals in line with the long half-lives (around 20 days) in paediatric patients and for higher treatment compliance,

Eligibility criteria: Inclusion Criteria:

* males and females in primary school children,
* anticipated local residence for the study duration,
* signed or thumb-printed informed consent by the parents or guardians and witnessed by an impartial witness (whenever parents/guardians are illiterate)

Exclusion Criteria:

* Children of the 6th primary school year
* Participation in any other investigational drug study (antimalarial or others) during the previous 30 days.
* Known hypersensitivity or serious adverse drug reaction (ADR) to the study drugs.
* Clinical malaria at baseline irrespectively of the severity (World Health Organisation malaria treatment guideline 2010) (Annex III).
* Febrile conditions caused by diseases other than malaria at first visit.
* Clinical symptoms of severe anaemia
* Illness or conditions like hematologic, cardiac, renal, hepatic diseases which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study, including known Glucose 6 phospahate dehydrogenase (G6PD) deficiency and sickle cell (SS form).
* Body weight \< 14 kg Children with major chronic infectious diseases (HIV, Tuberculosis, ...)

Primary outcomes:
measure: Hemoglobin change
timeFrame: Month 0-Month 12
Secondary outcomes:
measure: Change in mean Hb concentration at month 4 and 8 of follow-up
timeFrame: Month 0 - Month 4 - Month 8
measure: Prevalence of asymptomatic and clinical malaria at baseline & one year after enrolment;
timeFrame: Month 0 Month 12
measure: Prevalence of P. falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) gene mutations at baseline and at month 12 follow-up
timeFrame: Month 0 - Month 12
measure: Clinical (severe) malaria incidence and parasitaemia at month 4, 8, 12;
timeFrame: Month 4, 8 12
measure: Percentages of acute and severe malnourished at month 0, 4, 8, 12 through z-scores, W/H, H/A, and skinfolds
timeFrame: Month 0 - Month 12
measure: Educational achievement, at end of follow-up, and school attendance;
timeFrame: Month 0 - Month 12
measure: Prevalence and risk of environmental and host-related predictors for malaria (re)infections;
timeFrame: Month 0- Month 12
measure: adverse events
timeFrame: Month 0- Months 12
Other outcomes:
Locations:
city: Kinshasa
country: Congo
facility: Mokali health area of Biyela health zone, in Kinshasa province.
state: Kinshasa province
Study officials:
affiliation: University of Kinshasa
name: Junior Matangila, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Kinshasa
name: Pascal Lutumba, MD PhD
role: STUDY_DIRECTOR
affiliation: Universiteit Antwerpen
name: Joachim Doua, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Doua JY, Matangila J, Lutumba P, Van Geertruyden JP. Intermittent preventive treatment: efficacy and safety of sulfadoxine-pyrimethamine and sulfadoxine-pyrimethamine plus piperaquine regimens in schoolchildren of the Democratic Republic of Congo: a study protocol for a randomized controlled trial. Trials. 2013 Sep 24;14:311. doi: 10.1186/1745-6215-14-311.