Post-discharge Malaria Chemoprevention(PMC) Study

NCT ID: NCT02671175

Last Updated: 2020-06-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1049 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-20
• Study Completion Date: 2018-12-12

Brief Summary

This study evaluates the efficacy and safety of 3 months of malaria chemoprevention post-discharge using dihydroartemisinin piperaquine (DHA-P) in children under 5 years of age admitted with severe anemia. One half will receive monthly DHA-P and the other half placebo.

Detailed Description

Children hospitalized with severe anemia 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 with monthly 3-day treatment courses of artemether-lumefantrine (AL) in children with severe malarial anemia prevented 31% of deaths and readmissions. This study is a confirmatory efficacy trial in Kenya and Uganda to determine the efficacy and safety of malaria chemoprevention post-discharge. We hypothesize that an additional three months of malaria chemoprevention with monthly 3-day treatment courses with DHA-piperaquine (each providing about 4 weeks of post-treatment prophylaxis) provided during the post-discharge period to children recently admitted with severe anemia is superior to reduce all-cause readmission and mortality rates by 6 months compared with 2 weeks of post-treatment prophylaxis provided by the single course of oral AL when given as part of the standard in-hospital care around the time of discharge.

Conditions

Malaria; Severe Anemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

dihydroartemisinin-piperaquine

dihydroartemisinin-piperaquine (3-day treatment courses, given 2, 6, and 10 weeks after enrollment)

Group Type: ACTIVE_COMPARATOR

dihydroartemisinin-piperaquine

Intervention Type: DRUG

Children in both arms will receive standard in-hospital care for severe anaemia (blood transfusion, often combined with quinine or artesunate IV/IM). All children will then receive a 3-day course of AL (whether they initially had malaria or not), which will be started in-hospital as soon as they are able to take oral medication, and will be completed at home after discharge. At 2 weeks after enrolment surviving children will be randomized to receive either a standard 3-day courses of dihydroartemisinin-piperaquine (Eurartesim®, Sigma Tau, Italy) or an identical placebo regimen at 2, 6 and 10 weeks after enrolment.

dihydroartemisinin-piperaquine Placebo

Placebo comparator (matching tablets containing no active ingredients)

Group Type: PLACEBO_COMPARATOR

dihydroartemisinin-piperaquine placebo

Intervention Type: DRUG

Children will receive standard in-hospital care for severe anaemia (blood transfusion, often combined with quinine or artesunate IV/IM). All children will then receive a 3-day course of AL (whether they initially had malaria or not), which will be started in-hospital as soon as they are able to take oral medication, and will be completed at home after discharge. At 2 weeks after enrolment surviving children will be randomized to receive either a standard 3-day courses of dihydroartemisinin-piperaquine (Eurartesim®, Sigma Tau, Italy) or an identical placebo regimen at 2, 6 and 10 weeks after enrolment.

Interventions

dihydroartemisinin-piperaquine

Children in both arms will receive standard in-hospital care for severe anaemia (blood transfusion, often combined with quinine or artesunate IV/IM). All children will then receive a 3-day course of AL (whether they initially had malaria or not), which will be started in-hospital as soon as they are able to take oral medication, and will be completed at home after discharge. At 2 weeks after enrolment surviving children will be randomized to receive either a standard 3-day courses of dihydroartemisinin-piperaquine (Eurartesim®, Sigma Tau, Italy) or an identical placebo regimen at 2, 6 and 10 weeks after enrolment.

Intervention Type: DRUG

dihydroartemisinin-piperaquine placebo

Children will receive standard in-hospital care for severe anaemia (blood transfusion, often combined with quinine or artesunate IV/IM). All children will then receive a 3-day course of AL (whether they initially had malaria or not), which will be started in-hospital as soon as they are able to take oral medication, and will be completed at home after discharge. At 2 weeks after enrolment surviving children will be randomized to receive either a standard 3-day courses of dihydroartemisinin-piperaquine (Eurartesim®, Sigma Tau, Italy) or an identical placebo regimen at 2, 6 and 10 weeks after enrolment.

Intervention Type: DRUG

Other Intervention Names

Eurartesim; Eurartesim placebo

Eligibility Criteria

Inclusion Criteria

• Pre-study screening

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

2. Aged less than 59.5 months

3. Body weight >5 kg

4. Resident in catchment area Enrolment in study(t=0)

<!-- -->

1. Fulfilled the pre-study screening eligibility criteria

2. Aged < 59.5 months

3. Clinically stable, able to take oral medication

4. Subject completed blood transfusion(s) or became clinically stable without transfusion

5. Able to feed (for breastfeeding children) or eat (for older children)

6. Absence of know cardiac problems

7. Provision of informed consent by parent or guardian Randomisation (t=2 weeks)

<!-- -->

1. Fulfilled enrolment eligibility criteria and was enrolled during recent admission

2. Aged <60 months

3. Still clinically stable, able to take to oral medication, able to feed (for breastfeeding children) or eat (for older children) and able to sit unaided (for older children who were already able to do so prior to hospitalisation)

Exclusion Criteria

• Pre-study screening

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

2. Known sickle cell disease

3. Anticipated to reach the 5th birthday (60 months of age) within 2 weeks from enrolment (i.e. prior to randomization)

4. Child will reside for more than 25%of the 6 months study period (i.e. 6 weeks or more) outside of catchment area Enrolment in study (t=0)

<!-- -->

1. Previous enrolment in the present study

2. Known hypersensitivity to study drug

3. Sickle cell disease

4. Use or known need at the time of enrolment for concomitant prohibited medication during the 14 weeks PMC treatment period.

5. Ongoing or planned participation in another clinical trial involving ongoing or scheduled treatment with prohibited medicinal products or active follow-up during the course of the study (6 months from enrolment)

6. A known need at the time of enrolment for scheduled surgery during the subsequent course of the study (6 months from enrolment)

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

8. Know heart conditions, or family history of congenital prolongation of the QTc interval.

9. Taking medicinal products that are known to prolong the QTc interval Randomisation (t=2 weeks)

<!-- -->

1. Used dihydroartemisinin since enrolment

2. Use or known need at the time of randomisation for concomitant prohibited medication during the 14 weeks PMC treatment period.

3. Enrolled, or known agreement to enrol into another clinical trial involving ongoing or scheduled treatment with medicinal products during the course of the study (6 months from enrolment)

4. A known need at the time of randomisation for scheduled surgery during the subsequent course of the study (6 months from enrolment)

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

6. Withdrawal of consent since enrolment

• Maximum Eligible Age: 60 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Research Council of Norway

OTHER

Sponsor Role: collaborator

Kenya Medical Research Institute

OTHER

Sponsor Role: collaborator

Makerere University

OTHER

Sponsor Role: collaborator

Liverpool School of Tropical Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dr Titus K Kwambai, MSc

Role: PRINCIPAL_INVESTIGATOR

Liverpool School of Tropical Medicine

Dr Simon K Kariuki, PhD

Role: PRINCIPAL_INVESTIGATOR

Kenya Medical Research Institute

Dr Richard IDRO, PhD

Role: PRINCIPAL_INVESTIGATOR

Makerere University

Dr Robert Opoka, M.Med

Role: PRINCIPAL_INVESTIGATOR

Makerere University

Locations

Homa Bay County Referral Hospital

Homa Bay, Homa Bay County, Kenya

Migori County Referral Hospital

Migori, Migori County, Kenya

Siaya County Referral Hospital

Siaya, Siaya County, Kenya

Jaramogi Oginga Odinga Teaching and Referral Hospital

Kisumu, , Kenya

Hoima Regional Referral Hospital

Hoima, , Uganda

Jinja Regional Referral Hospital

Jinja, , Uganda

Kamuli Mission Hospital

Kamuli, , Uganda

Masaka Regional Referral Hospital

Masaka, , Uganda

Mubende Regional Referral Hospital:

Mubende, , Uganda

Countries

Kenya; Uganda

References

Kwambai TK, Dhabangi A, Idro R, Opoka R, Watson V, Kariuki S, Kuya NA, Onyango ED, Otieno K, Samuels AM, Desai MR, Boele van Hensbroek M, Wang D, John CC, Robberstad B, Phiri KS, Ter Kuile FO. Malaria Chemoprevention in the Postdischarge Management of Severe Anemia. N Engl J Med. 2020 Dec 3;383(23):2242-2254. doi: 10.1056/NEJMoa2002820.

Reference Type: DERIVED

PMID: 33264546 (View on PubMed)

Kwambai TK, Dhabangi A, Idro R, Opoka R, Kariuki S, Samuels AM, Desai M, van Hensbroek MB, John CC, Robberstad B, Wang D, Phiri K, Ter Kuile FO. Malaria chemoprevention with monthly dihydroartemisinin-piperaquine for the post-discharge management of severe anaemia in children aged less than 5 years in Uganda and Kenya: study protocol for a multi-centre, two-arm, randomised, placebo-controlled, superiority trial. Trials. 2018 Nov 6;19(1):610. doi: 10.1186/s13063-018-2972-1.

Reference Type: DERIVED

PMID: 30400934 (View on PubMed)

Other Identifiers

2965

Identifier Type: OTHER

Identifier Source: secondary_id

2015-125

Identifier Type: OTHER

Identifier Source: secondary_id

2014/1911

Identifier Type: OTHER

Identifier Source: secondary_id

14.034

Identifier Type: -

Identifier Source: org_study_id