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

NCT ID: NCT02721420

Last Updated: 2018-02-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 375 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-24
• Study Completion Date: 2019-12-31

Brief 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.

Detailed 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

Conditions

Malaria; Severe Anemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Drug + short message(SMS) reminder

dihydroartemesinin-piperaquine (3-day treatment courses, given 2, 6, and 10 weeks after enrolment) with SMS reminders prior to each treatment course

Group Type: OTHER

dihydroartemisinin-piperaquine

Intervention Type: DRUG

short message(SMS) reminder

Intervention Type: OTHER

Drug + no short message(SMS) reminder

dihydroartemisinin-piperaquine (3-day treatment courses, given 2, 6, and 10 weeks after enrolment) without SMS reminders prior to each treatment course.

Group Type: OTHER

dihydroartemisinin-piperaquine

Intervention Type: DRUG

Drug+ Health worker reminder

dihydroartemisinin-piperaquine (3-day treatment courses, given 2, 6, and 10 weeks after enrolment) with Health surveillance assistants reminders prior to each treatment course.

Group Type: OTHER

dihydroartemisinin-piperaquine

Intervention Type: DRUG

Health worker reminder

Intervention Type: OTHER

Health surveillance assistants reminders prior to each treatment course

Drug at hospital + SMS reminder

dihydroartemisinin-piperaquine (3-day treatment courses, given 2, 6, and 10 weeks after enrolment) collected at the outpatient department without an SMS reminders prior to each treatment course.

Group Type: OTHER

dihydroartemisinin-piperaquine

Intervention Type: DRUG

Drug at Hospital+no SMS reminder

dihydroartemisinin-piperaquine (3-day treatment courses, given 2, 6, and 10 weeks after enrolment) collected at the outpatient department with a short message reminder prior to each treatment course

Group Type: OTHER

dihydroartemisinin-piperaquine

Intervention Type: DRUG

message(SMS) reminder

Intervention Type: OTHER

Interventions

dihydroartemisinin-piperaquine

Intervention Type: DRUG

message(SMS) reminder

Intervention Type: OTHER

Health worker reminder

Health surveillance assistants reminders prior to each treatment course

Intervention Type: OTHER

short message(SMS) reminder

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 4 Months
• Maximum Eligible Age: 59 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Bergen

OTHER

Sponsor Role: collaborator

The Research Council of Norway

OTHER

Sponsor Role: collaborator

Makerere University

OTHER

Sponsor Role: collaborator

Liverpool School of Tropical Medicine

OTHER

Sponsor Role: collaborator

Kenya Medical Research Institute

OTHER

Sponsor Role: collaborator

University of Amsterdam

OTHER

Sponsor Role: collaborator

Imperial College London

OTHER

Sponsor Role: collaborator

London School of Hygiene and Tropical Medicine

OTHER

Sponsor Role: collaborator

University of Minnesota

OTHER

Sponsor Role: collaborator

Ministry of Health and Population, Malawi

OTHER_GOV

Sponsor Role: collaborator

Ministry of Health, Malawi

OTHER_GOV

Sponsor Role: collaborator

Kamuzu University of Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kamija Phiri, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Malawi

Locations

College Of Medicine,Training and Research Unit Of Excellence,Zomba Central Hospital

Zomba, , Malawi

Site Status: RECRUITING

Countries

Malawi

Central Contacts

Kamija Phiri, PhD

Role: CONTACT

kphiri@medcol.mw

+265999957048

Thandile Nkosi-Gondwe, MBBS

Role: CONTACT

tgondwe@medcol.mw

+265995508830

Facility Contacts

Thandile Nkosi-Gondwe, MBBS

Role: primary

tgondwe@medcol.mw

+265995508830

Kamija Phiri, PhD

Role: backup

kphiri@medcol.mw

+265999957048

References

Nkosi-Gondwe T, Robberstad B, Mukaka M, Idro R, Opoka RO, Banda S, Kuhl MJ, O Ter Kuile F, Blomberg B, Phiri KS. Adherence to community versus facility-based delivery of monthly malaria chemoprevention with dihydroartemisinin-piperaquine for the post-discharge management of severe anemia in Malawian children: A cluster randomized trial. PLoS One. 2021 Sep 10;16(9):e0255769. doi: 10.1371/journal.pone.0255769. eCollection 2021.

Reference Type: DERIVED

PMID: 34506503 (View on PubMed)

Nkosi-Gondwe T, Robberstad B, Blomberg B, Phiri KS, Lange S. Introducing post-discharge malaria chemoprevention (PMC) for management of severe anemia in Malawian children: a qualitative study of community health workers' perceptions and motivation. BMC Health Serv Res. 2018 Dec 19;18(1):984. doi: 10.1186/s12913-018-3791-5.

Reference Type: DERIVED

PMID: 30567567 (View on PubMed)

Gondwe T, Robberstad B, Mukaka M, Lange S, Blomberg B, Phiri K. Delivery strategies for malaria chemoprevention with monthly dihydroartemisinin-piperaquine for the post-discharge management of severe anaemia in children aged less than 5 years old in Malawi: a protocol for a cluster randomized trial. BMC Pediatr. 2018 Jul 20;18(1):238. doi: 10.1186/s12887-018-1199-3.

Reference Type: DERIVED

PMID: 30029620 (View on PubMed)

Svege S, Kaunda B, Robberstad B, Nkosi-Gondwe T, Phiri KS, Lange S. Post-discharge malaria chemoprevention (PMC) in Malawi: caregivers; acceptance and preferences with regard to delivery methods. BMC Health Serv Res. 2018 Jul 11;18(1):544. doi: 10.1186/s12913-018-3327-z.

Reference Type: DERIVED

PMID: 29996833 (View on PubMed)

Other Identifiers

P.02/15/1679

Identifier Type: -

Identifier Source: org_study_id