Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02671175
Other study ID # 14.034
Secondary ID 29652015-1252014
Status Completed
Phase Phase 3
First received
Last updated
Start date May 20, 2016
Est. completion date December 12, 2018

Study information

Verified date June 2020
Source Liverpool School of Tropical Medicine
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 1049
Est. completion date December 12, 2018
Est. primary completion date October 24, 2018
Accepts healthy volunteers No
Gender All
Age group N/A to 60 Months
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

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.
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.

Locations

Country Name City State
Kenya Homa Bay County Referral Hospital Homa Bay Homa Bay County
Kenya Jaramogi Oginga Odinga Teaching and Referral Hospital Kisumu
Kenya Migori County Referral Hospital Migori Migori County
Kenya Siaya County Referral Hospital Siaya Siaya County
Uganda 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

Sponsors (4)

Lead Sponsor Collaborator
Liverpool School of Tropical Medicine Kenya Medical Research Institute, Makerere University, The Research Council of Norway

Countries where clinical trial is conducted

Kenya,  Uganda, 

Outcome

Type Measure Description Time frame Safety issue
Primary All-cause deaths or all-cause re-admissions by 26 weeks from randomization (composite primary outcome). Primary outcome 6 months
Secondary 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 26 weeks from randomization
Secondary All-cause readmission by 26 weeks from randomization 26 weeks from randomization
Secondary 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 26 weeks from randomization
Secondary Readmission due to severe malarial anaemia (severe anaemia plus parenteral or oral antimalarial treatment)by 26 weeks from randomization 26 from randomization
Secondary Readmission due to severe anaemia or severe malaria (composite outcome)by 26 weeks from randomization 26 weeks from randomization
Secondary All-cause mortality by 26 weeks from randomization 26 weeks from randomization
Secondary Clinic visits because of smear of rapid diagnostic test (RDT) confirmed non-severe malaria by 26 weeks from randomization 26 weeks from randomization
Secondary 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 26 weeks from randomization
Secondary Readmission due to severe disease other than severe anaemia and severe malaria by 26 weeks from randomization 26 weeks from randomization
Secondary Non-severe all-cause sick-child clinic visits by 26 weeks from randomization 26 weeks from randomization
Secondary Non-malaria sick child clinic visits by 26 weeks from randomization 26 weeks from randomization
Secondary Malaria infection at 6 month 6 month
Secondary Hb at 6 months 6 months
Secondary 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 6 months
Secondary Weight-for-age, height-for-age, and height-for-weight Z-scores, standard deviation (SD) scores of reference population) at 6 months 6 months
Secondary Serious adverse events, excluding primary and secondary efficacy outcomes, by 26 weeks from randomization 26 weeks from randomization
Secondary Serious adverse events within 7 days after the start of each course of PMC, excluding primary and secondary efficacy outcomes. 26 weeks from randomization
Secondary Adverse events by 26 weeks from randomization 26 weeks from randomization
Secondary Adverse events within 7 days after start of each course of PMC. 7 days post drug administration
Secondary Corrected QT interval (QTc) prolongation measured by electro cardio gram (ECG)4-6 hours after 3rd dose of each course 4-6 hours after 3rd dose of each course
Secondary Patients costs of receiving the intervention 26 weeks after randomization
Secondary Patients costs related to treatment of the primary disease, readmission or death 26 weeks after randomization
Secondary The costs of the health care system of providing the intervention 26 weeks after randomization
Secondary The costs of the health system of treating the primary disease and anaemia, as well as treatment of readmissions or costs related to fatalities 26 weeks after randomization
See also
  Status Clinical Trial Phase
Completed NCT04601714 - Baseline Cohort Malaria Morbidity Study
Withdrawn NCT04020653 - A Study to Assess the Safety and Efficacy of 5-aminolevulinic Acid Hydrochloride (5-ALA HCl) and Sodium Ferrous Citrate (SFC) Added on Artemisinin-based Combination Therapy (ACT) in Adult Patients With Uncomplicated Malaria Phase 2
Terminated NCT04368910 - Safety and Efficacy of Pyronaridine Artesunate Vs Chloroquine in Children and Adult Patients With Acute Vivax Malaria Phase 3
Completed NCT03641339 - Defining Skin Immunity of a Bite of Key Insect Vectors in Humans N/A
Completed NCT02544048 - Markers of T Cell Suppression: Antimalarial Treatment and Vaccine Responses in Healthy Malian Adults
Completed NCT00527163 - Role of Nitric Oxide in Malaria
Not yet recruiting NCT05934318 - L-ArGinine to pRevent advErse prEgnancy Outcomes (AGREE) N/A
Active, not recruiting NCT04704674 - Community Dynamics of Malaria Transmission in Humans and Mosquitoes in Fleh-la and Marshansue, Salala District, Bong County, Liberia
Completed NCT03276962 - Efficacy, Safety and Immunogenicity Study of GSK Biologicals' Candidate Malaria Vaccine (SB257049) Evaluating Schedules With or Without Fractional Doses, Early Dose 4 and Yearly Doses, in Children 5-17 Months of Age Phase 2
Completed NCT04966871 - Safety, Tolerability and Efficacy of PfSPZ Vaccine Against Heterologous CHMI in US Malaria naïve Adults Phase 1
Completed NCT00289185 - Study of Safety, Immunogenicity and Efficacy of a Candidate Malaria Vaccine in Tanzanian Infants Phase 2
Recruiting NCT03937817 - Collection of Human Biospecimens for Basic and Clinical Research Into Globin Variants
Active, not recruiting NCT06153862 - Africa Ready Malaria Screening N/A
Completed NCT04545905 - Antenatal Care as a Platform for Malaria Surveillance: Utilizing Community Prevalence Measures From the New Nets Project to Validate ANC Surveillance of Malaria in Burkina Faso
Recruiting NCT06278181 - Diabetes, Metabolic Syndrome and Risk of Malaria in Cameroon
Completed NCT02909712 - Cardiac Safety of Dihydroartemisinin-Piperaquine Amongst Pregnant Women in Tanzania Phase 2
Withdrawn NCT02793388 - A Trial on Supervised Primaquine Use in Ethiopia Phase 4
Withdrawn NCT02793414 - Diagnostic Utility of Volatile Organic Compounds in Human Breath for Acute Clinical Malaria in Ethiopia
Completed NCT02793622 - Prevention of Malaria in HIV-uninfected Pregnant Women and Infants Phase 3
Completed NCT02536222 - Accelerating the Reduction of Malaria Transmission in Kanel, Ranérou and Linguère Districts Phase 4