Delivery of Malaria Chemoprevention in the Post-discharge Management of Children With Severe Anaemia in Malawi

Malaria Clinical Trial

— PMC  

Official title:

Malaria Chemoprevention With Monthly Treatment With Dihydroartemisinin-Piperaquine for the Post-discharge Management of Severe Anaemia in Children Less Than 5 Years in Malawi

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02721420
• Other study ID #: P.02/15/1679
• Status: Recruiting
• Phase: Phase 3
• First received: February 13, 2016
• Last updated: January 30, 2018
• Start date: March 24, 2016
• Est. completion date: December 2019

Study information

• Verified date: January 2018
• Source: University of Malawi College of Medicine
• Contact: Kamija Phiri, PhD
• Phone: +265999957048
• Email: kphiri[@]medcol.mw
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Background and rationale: Children hospitalised with severe anaemia in Africa are at high risk of readmission or death within 6 months after discharge. No strategy specifically addresses this post-discharge period. In Malawi, 3 months of post-discharge malaria chemoprevention (PMC) with monthly 3-day treatment courses of artemether-lumefantrine (AL) in children with severe malarial anaemia prevented 31% of deaths and readmissions. The effect was in addition to the effect of insecticide-treated bednets. There is now need to design and evaluate effective delivery mechanism for PMC within the health system.

Description:

Objectives: The primary objective of the trial is to determine the optimum PMC delivery mechanism by comparing community- versus health facility-based strategies in order to inform policy.

Study Type: This is a single-centre, matched, cluster randomized, 5-arm, factorial design trial comparing the uptake of PMC-DHP delivered through health facility or community-based approaches with or without SMS/HSA reminders.

Site: 90 villages in the catchment areas of Zomba Central hospital in southern Malawi

Study Population:

Inclusion criteria: convalescent children aged less than 5 years and weighing >5 kg admitted with severe anaemia (haemoglobin<5g/dL / Ht<15%); clinically stable, able to take or switch to oral medication; post-transfusion Hb >5g/dL.

Exclusion criteria: blood loss due to trauma, malignancy, known bleeding disorders or sickle cell trait, known hypersensitivity to study drug, known heart conditions, non-resident in study area, previous participation in study, known need at enrolment for prohibited medication and scheduled surgery during the course of the study. HIV infection and cotrimoxazole prophylaxis are not exclusion criteria

Study Interventions:

All children will receive Dihydroartemisinin-piperaquine (3-day treatment courses, given 2,6 and 10 weeks after discharge) either:

1. at discharge + SMS Reminder;

2. at discharge + No SMS Reminder;

3. at discharge + HSA Reminder;

4. at OPD + SMS Reminder; or

5. at OPD + No SMS Reminder

Outcome Measures:

Primary: 100% of PMC drugs uptake (defined as administration of all 3-day treatment courses, given 2, 6 and 10 weeks after discharge) assessed by unannounced spot checks.

Follow-up procedures: Children will be followed up for 15 weeks by passive case detection in 2 phases: Pre-PMC (2 weeks between hospital admission and 2 weeks post-discharge); PMC (2-14 weeks post-discharge)

Sample Size: A sample size of 75 children per arm (375 total children) allows for a detection of 25% increase in uptake from 50% to 75% with 10% loss to follow-up (power 90%, α=0.05).

Data Analysis: The % of children receiving IPTpd according to schedule will be compared by relative risks (95% CI), adjusted for prognostic factors at baseline using log binomial or Poisson regression with adjustment for cluster effects

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 375
• Est. completion date: December 2019
• Est. primary completion date: March 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Months to 59 Months

Eligibility

Inclusion Criteria:

1. Haemoglobin <5.0g/dl or PCV <15%, or requirement for blood transfusion for other clinical reasons on or during admission to the hospital

2. Age between 4 months (inclusive) and 59 months (inclusive)

3. Body weight >5kgs

Screening (in-hospital):

1. Fulfilled the pre-study screening eligibility criteria

2. Clinically stable, able to switch to oral medication

3. Subject completed blood transfusion(s) in accordance with routine hospital practice

4. Able to feed (for breastfed children) or eat (for older children)

5. Absence of known cardiac problems

6. Provision of informed consent by parent or guardian

Randomization (at discharge):

1. Fulfilled screening eligibility criteria

2. Still clinically stable, able to take oral medication, able to feed (for breastfed children) or eat (for older children) and able to sit unaided (for older children who were able to do so prior to hospitalization

Exclusion Criteria:

1. Recognised specific other cause of severe anaemia (e.g. trauma, haematological malignancy, known bleeding disorder)

2. Known sickle cell

3. Child will reside for more than 25% of the 3.5months study period (i.e. 3 weeks or more) outside of catchment area Enrolment in the study (t=0) at discharge

4. Previous enrolment in the present study

5. Known hypersensitivity to study drug

6. Sickle cell disease

7. Known need at the time of enrolment for concomitant prohibited medication during the 14 weeks PMC treatment period.

8. On-going or planned participation into another clinical trial involving on-going or scheduled treatment with medicinal products during the course of the study (3.5 months from enrolment)

9. Known need, or scheduled surgery during the course of the study (3.5 months)

10. Suspected non-compliance with the follow-up schedule

11. Known heart conditions, or family history of congenital prolongation of the QTc interval

Related Conditions & MeSH terms

• Anemia
• Malaria
• Severe Anemia

Intervention

Drug:
• dihydroartemisinin-piperaquine

Other:
• message(SMS) reminder

• Health worker reminder
Health surveillance assistants reminders prior to each treatment course
• short message(SMS) reminder

Locations

Country	Name	City	State
Malawi	College Of Medicine,Training and Research Unit Of Excellence,Zomba Central Hospital	Zomba

Sponsors (12)

Lead Sponsor	Collaborator
University of Malawi College of Medicine	Imperial College London, Kenya Medical Research Institute, Liverpool School of Tropical Medicine, London School of Hygiene and Tropical Medicine, Makerere University, Ministry of Health and Population, Malawi, Ministry of Health, Malawi, The Research Council of Norway, University of Amsterdam, University of Bergen, University of Minnesota, MN

Country where clinical trial is conducted

Malawi, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	All-causes of deaths and all-causes of hospital re-admissions during the 15 week trial period.	Assessment of all children who die or are hospitalised during the trial period	15 weeks
Other	Assessment of the added costs of the interventions to the health system and the individual patients by conducting interviews during the 15 week trial period.		15 weeks
Other	Assessment of how the study interventions are acceptable by patients and health workers by conducting focus group discussions and using self administered questionnaires during the 15 week trial period.		15 weeks
Primary	Proportion of those with 100 % uptake of PMC drugs during the 15 weeks of the study period.	100 % uptake is defined as administration of all study drugs and compliance to study visits during the course of 15 weeks.	15 weeks
Secondary	Proportion of those with 60% uptake of PMC drugs during the 15 weeks of the study period.	60 % uptake is defined as administration of 6 or more [but less than 9] of the daily dosages out of the total of 9 during the 15 week study period.	15 weeks
Secondary	Proportion of those with 30 % uptake of PMC drugs during the 15 week trial period.	30 % PMC uptake is defined as administration of 3 or more [but less than 6] of the daily dosages out of the total of 9 during the 15 week trial period.	15 weeks
Secondary	Proportion of those with <30% uptake of PMC drugs during the 15 week trial period.	<30 % PMC uptake is defined as administration of less than 3 of the daily dosages out of the total of 9 assessed during the 15 week trial period.	15 weeks