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Post-discharge Malaria Chemoprevention(PMC) Study (PMC)

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ClinicalTrials.gov Identifier: NCT02671175
Recruitment Status : Recruiting
First Posted : February 2, 2016
Last Update Posted : October 6, 2016
Sponsor:
Collaborators:
The Research Council of Norway
Kenya Medical Research Institute
Makerere University
Information provided by (Responsible Party):
Liverpool School of Tropical Medicine

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.

Condition or disease Intervention/treatment Phase
Malaria Severe Anemia Drug: dihydroartemisinin-piperaquine Drug: dihydroartemisinin-piperaquine placebo Phase 3

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2212 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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
Study Start Date : May 2016
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : March 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anemia Malaria

Arm Intervention/treatment
Active Comparator: dihydroartemisinin-piperaquine
dihydroartemisinin-piperaquine (3-day treatment courses, given 2, 6, and 10 weeks after enrollment)
Drug: 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.
Other Name: Eurartesim

Placebo Comparator: dihydroartemisinin-piperaquine Placebo
Placebo comparator (matching tablets containing no active ingredients)
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.
Other Name: Eurartesim placebo




Primary Outcome Measures :
  1. All-cause deaths or all-cause re-admissions by 26 weeks from randomization (composite primary outcome). [ Time Frame: 6 months ]

Secondary Outcome Measures :
  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 [ Time Frame: 26 weeks from randomization ]
  2. 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 [ Time Frame: 26 weeks from randomization ]
  3. Readmission due to severe malarial anaemia (severe anaemia plus parenteral or oral antimalarial treatment)by 26 weeks from randomization [ Time Frame: 26 from randomization ]
  4. Readmission due to severe anaemia or severe malaria (composite outcome)by 26 weeks from randomization [ Time Frame: 26 weeks from randomization ]
  5. All-cause mortality by 26 weeks from randomization [ Time Frame: 26 weeks from randomization ]
  6. Clinic visits because of smear of rapid diagnostic test (RDT) confirmed non-severe malaria by 26 weeks from randomization [ Time Frame: 26 weeks from randomization ]
  7. 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 [ Time Frame: 26 weeks from randomization ]
  8. Readmission due to severe disease other than severe anaemia and severe malaria by 26 weeks from randomization [ Time Frame: 26 weeks from randomization ]
  9. Non-severe all-cause sick-child clinic visits by 26 weeks from randomization [ Time Frame: 26 weeks from randomization ]
  10. Non-malaria sick child clinic visits by 26 weeks from randomization [ Time Frame: 26 weeks from randomization ]
  11. Malaria infection at 6 month [ Time Frame: 6 month ]
  12. Hb at 6 months [ Time Frame: 6 months ]
  13. 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 [ Time Frame: 6 months ]
  14. Weight-for-age, height-for-age, and height-for-weight Z-scores, standard deviation (SD) scores of reference population) at 6 months [ Time Frame: 6 months ]
  15. Serious adverse events, excluding primary and secondary efficacy outcomes, by 26 weeks from randomization [ Time Frame: 26 weeks from randomization ]
  16. Serious adverse events within 7 days after the start of each course of PMC, excluding primary and secondary efficacy outcomes. [ Time Frame: 26 weeks from randomization ]
  17. Adverse events by 26 weeks from randomization [ Time Frame: 26 weeks from randomization ]
  18. Adverse events within 7 days after start of each course of PMC. [ Time Frame: 7 days post drug administration ]
  19. Corrected QT interval (QTc) prolongation measured by electro cardio gram (ECG)4-6 hours after 3rd dose of each course [ Time Frame: 4-6 hours after 3rd dose of each course ]
  20. Patients costs of receiving the intervention [ Time Frame: 26 weeks after randomization ]
  21. Patients costs related to treatment of the primary disease, readmission or death [ Time Frame: 26 weeks after randomization ]
  22. The costs of the health care system of providing the intervention [ Time Frame: 26 weeks after randomization ]
  23. The costs of the health system of treating the primary disease and anaemia, as well as treatment of readmissions or costs related to fatalities [ Time Frame: 26 weeks after randomization ]


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Ages Eligible for Study:   up to 60 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02671175


Contacts
Contact: Prof F Kuile, PhD +447846377369 feiko.terkuile@lstmed.ac.uk
Contact: Dr Titus K Kwambai, MSc +254723354238 titus.kwambai@lstmed.ac.uk

Locations
Kenya
Homa Bay County Referral Hospital Recruiting
Homa Bay, Homa Bay County, Kenya, 40100
Contact: Dr Titus k Kwambai, MSc    +254723354238    titus.kwambai@lstmed.ac.uk   
Migori County Referral Hospital Recruiting
Migori, Migori County, Kenya, 40400
Contact: Dr Grace M Nalwa, M.Med    +254722263041    gmnalwa@gmail.com   
Contact: Dr Titus K Kwambai    +254723354238    titus.kwambai@lstmed.ac.uk   
Siaya County Referral Hospital Recruiting
Siaya, Siaya County, Kenya, 40100
Contact: Dr. Titus K Kwambai, MSc    +254723354238    titus.kwambai@lstmed.ac.uk   
Uganda
Hoima Regional Referral Hospital Recruiting
Hoima, Uganda
Contact: Dr Tom D Ediamu, M.Med    +25677471388    Didimus@yahoo.com   
Contact: Dr Aggrey Dhabangi, M.Med    +256772833789    adhabangi@gmail.com   
Jinja Regional Referral Hospital Recruiting
Jinja, Uganda
Contact: Dr Harriet L Nambuya, M.Med    +256772448247    nambuyaharriet@yahoo.com   
Contact: Dr Aggrey Dhabangi, M.Med    +256772833789    adhabangi@gmail.com   
Masaka Regional Referral Hospital Recruiting
Masaka, Uganda
Contact: Dr Aggrey Dhabangi, M.Med    +256772833789    adhabangi@gmail.com   
Sponsors and Collaborators
Liverpool School of Tropical Medicine
The Research Council of Norway
Kenya Medical Research Institute
Makerere University
Investigators
Principal Investigator: Dr Titus K Kwambai, MSc Liverpool School of Tropical Medicine
Principal Investigator: Dr Simon K Kariuki, PhD Kenya Medical Research Institute
Principal Investigator: Dr Richard IDRO, PhD Makerere University
Principal Investigator: Dr Robert Opoka, M.Med Makerere University

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Liverpool School of Tropical Medicine
ClinicalTrials.gov Identifier: NCT02671175     History of Changes
Other Study ID Numbers: 14.034
2965 ( Other Identifier: Kenya Medical Research Institute )
2015-125 ( Other Identifier: Uganda REC )
2014/1911 ( Other Identifier: Norway REC )
First Posted: February 2, 2016    Key Record Dates
Last Update Posted: October 6, 2016
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual, de-identified participant data will be made available for meta-analyses as soon as the data analysis is completed, with the understanding that results of the meta-analysis will not be published prior to the results of the individual trial without prior agreement of the investigators. No later than 5 years after the publication of the trial a fully de-identified data set will be available for sharing purposes

Additional relevant MeSH terms:
Anemia
Malaria
Hematologic Diseases
Protozoan Infections
Parasitic Diseases
Piperaquine
Dihydroartemisinin
Artemisinins
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents