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MalariaPhase 3PMCNCT02671175

Post-discharge Malaria Chemoprevention(PMC) Study

A Phase 3 study testing dihydroartemisinin-piperaquine in people with Malaria and Severe Anemia, run by Liverpool School of Tropical Medicine at 9 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages Up to 60 months
Conditions the study is for
Malaria, Severe Anemia
What is being tested?
dihydroartemisinin-piperaquine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,049 participants
Where
9 sitesin 2 countries
Study dates
20 May 2016to 12 Dec 2018
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 60 months
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Pre-study screening
  • Haemoglobin <5.0 g/dl or PCV < 15%, or requirement for blood transfusion for other clinical reasons on or during admission to the hospital
  • Aged less than 59.5 months
  • Body weight >5 kg
  • Resident in catchment area Enrolment in study(t=0)
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  • Fulfilled the pre-study screening eligibility criteria
  • Aged < 59.5 months
  • Clinically stable, able to take oral medication
  • Subject completed blood transfusion(s) or became clinically stable without transfusion
  • Able to feed (for breastfeeding children) or eat (for older children)
  • Absence of know cardiac problems
  • Provision of informed consent by parent or guardian Randomisation (t=2 weeks)
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  • Fulfilled enrolment eligibility criteria and was enrolled during recent admission
  • Aged <60 months
  • 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)

Who cannot join

  • Pre-study screening
  • Recognised specific other cause of severe anaemia (e.g. trauma, haematological malignancy, known bleeding disorder)
  • Known sickle cell disease
  • Anticipated to reach the 5th birthday (60 months of age) within 2 weeks from enrolment (i.e. prior to randomization)
  • 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)
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  • Previous enrolment in the present study
  • Known hypersensitivity to study drug
  • Sickle cell disease
  • Use or known need at the time of enrolment for concomitant prohibited medication during the 14 weeks PMC treatment period.
  • 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)
  • A known need at the time of enrolment for scheduled surgery during the subsequent course of the study (6 months from enrolment)
  • Suspected non-compliance with the follow-up schedule
  • Know heart conditions, or family history of congenital prolongation of the QTc interval.
  • Taking medicinal products that are known to prolong the QTc interval Randomisation (t=2 weeks)
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  • Used dihydroartemisinin since enrolment
  • Use or known need at the time of randomisation for concomitant prohibited medication during the 14 weeks PMC treatment period.
  • 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)
  • A known need at the time of randomisation for scheduled surgery during the subsequent course of the study (6 months from enrolment)
  • Suspected non-compliance with the follow-up schedule
  • Withdrawal of consent since enrolment

Trial locations and contacts

9 sites in 2 countries.

9 sites in 2 countries

Uganda5 sites

  • Hoima Regional Referral Hospital

    Hoima

  • Jinja Regional Referral Hospital

    Jinja

  • Kamuli Mission Hospital

    Kamuli

  • Masaka Regional Referral Hospital

    Masaka

  • Mubende Regional Referral Hospital:

    Mubende

Other trials in Uganda

Kenya4 sites

  • Homa Bay County Referral Hospital

    Homa Bay, Homa Bay County, 40100

  • Jaramogi Oginga Odinga Teaching and Referral Hospital

    Kisumu

  • Migori County Referral Hospital

    Migori, Migori County, 40400

  • Siaya County Referral Hospital

    Siaya, Siaya County, 40100

Other trials in Kenya

About this study

Official title: Malaria Chemoprevention With Monthly Treatment With Dihydroartemisinin-piperaquine for the Post-discharge Management of Severe Anaemia in Children Aged Less Than 5 Years in Uganda and Kenya: A Two-arm Randomised Placebo Controlled Trial

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.

Read the 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.

Being tested
dihydroartemisinin-piperaquine, dihydroartemisinin-piperaquine placebo
Medical subject headings
Malaria, Anemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • dihydroartemisinin-piperaquineDrug

    Also called Eurartesim

    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 placeboDrug

    Also called Eurartesim 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.

Study groups in NCT02671175
Study groupRoleWhat they receive
dihydroartemisinin-piperaquineActive comparatordihydroartemisinin-piperaquine (3-day treatment courses, given 2, 6, and 10 weeks after enrollment)
Receives: Drug: dihydroartemisinin-piperaquine
dihydroartemisinin-piperaquine PlaceboPlacebo comparatorPlacebo comparator (matching tablets containing no active ingredients)
Receives: Drug: dihydroartemisinin-piperaquine placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. All-cause deaths or all-cause re-admissions by 26 weeks from randomization (composite primary outcome).

    Primary outcome

    Measured: 6 months

Secondary outcomes (24)

  1. Readmission due to severe malaria (defined as any treatment with parenteral quinine or artesunate, or presence of severe anaemia and treatment with oral antimalarials) by 26 weeks from randomization

    Measured: 26 weeks from randomization

  2. All-cause readmission by 26 weeks from randomization

    Measured: 26 weeks from randomization

  3. Readmissions due to severe anaemia (defined as Haemoglobin (Hb) <5g/dL or packed-cell volume (PCV) <15% or requirement for blood transfusion based on other clinical indication)by 26 weeks from randomization

    Measured: 26 weeks from randomization

  4. Readmission due to severe malarial anaemia (severe anaemia plus parenteral or oral antimalarial treatment)by 26 weeks from randomization

    Measured: 26 from randomization

  5. Readmission due to severe anaemia or severe malaria (composite outcome)by 26 weeks from randomization

    Measured: 26 weeks from randomization

  6. All-cause mortality by 26 weeks from randomization

    Measured: 26 weeks from randomization

  7. Clinic visits because of smear of rapid diagnostic test (RDT) confirmed non-severe malaria by 26 weeks from randomization

    Measured: 26 weeks from randomization

  8. Readmission due to severe malaria-specific anaemia (severe anaemia plus parenteral or oral antimalarial treatment and parasite density >5000/microlitre) by 26 weeks from randomization

    Measured: 26 weeks from randomization

  9. Readmission due to severe disease other than severe anaemia and severe malaria by 26 weeks from randomization

    Measured: 26 weeks from randomization

  10. Non-severe all-cause sick-child clinic visits by 26 weeks from randomization

    Measured: 26 weeks from randomization

  11. Non-malaria sick child clinic visits by 26 weeks from randomization

    Measured: 26 weeks from randomization

  12. Malaria infection at 6 month

    Measured: 6 month

  13. Hb at 6 months

    Measured: 6 months

  14. Any anaemia (Hb<11 g/dL), mild anaemia (Hb 8.0-10.99 g/dl) moderate anaemia (Hb 5.0-7.99 g/dL) and severe anaemia (Hb<5 g/dL) at 6 months

    Measured: 6 months

  15. Weight-for-age, height-for-age, and height-for-weight Z-scores, standard deviation (SD) scores of reference population) at 6 months

    Measured: 6 months

  16. Serious adverse events, excluding primary and secondary efficacy outcomes, by 26 weeks from randomization

    Measured: 26 weeks from randomization

  17. Serious adverse events within 7 days after the start of each course of PMC, excluding primary and secondary efficacy outcomes.

    Measured: 26 weeks from randomization

  18. Adverse events by 26 weeks from randomization

    Measured: 26 weeks from randomization

  19. Adverse events within 7 days after start of each course of PMC.

    Measured: 7 days post drug administration

  20. Corrected QT interval (QTc) prolongation measured by electro cardio gram (ECG)4-6 hours after 3rd dose of each course

    Measured: 4-6 hours after 3rd dose of each course

  21. Patients costs of receiving the intervention

    Measured: 26 weeks after randomization

  22. Patients costs related to treatment of the primary disease, readmission or death

    Measured: 26 weeks after randomization

  23. The costs of the health care system of providing the intervention

    Measured: 26 weeks after randomization

  24. The costs of the health system of treating the primary disease and anaemia, as well as treatment of readmissions or costs related to fatalities

    Measured: 26 weeks after randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Feb 2016 (estimated)
  2. Study start20 May 2016
  3. Primary completion24 Oct 2018
  4. Study completion12 Dec 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,049 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02671175
Sponsor's protocol ID
14.034
Other IDs
2965, 2015-125, 2014/1911
Acronym
PMC
Status last verified
Jun 2020
First submitted
28 Jan 2016
Last updated
4 Jun 2020
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Yes: All individual-participant data collected during this trial will be stored in a public data repository after de-identification. Data and documents, including the study protocol, and the statistical analysis plan, will be made available and access to data provided when a proposal has been approved by the investigators, after consideration of overlap between the proposal and any ongoing efforts. Data will be available beginning at three months after publication of this Article.

Publications

  • 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.

    PubMed 33264546

  • 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.

    PubMed 30400934

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing dihydroartemisinin-piperaquine in people with Malaria and Severe Anemia, run by Liverpool School of Tropical Medicine at 9 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Uganda, Kenya. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

All-cause deaths or all-cause re-admissions by 26 weeks from randomization (composite primary outcome). (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02671175, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2020; AzTrials last refreshed its copy on 30 Oct 2026.

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