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Dihydroartemisinin-Piperaquine or Sulphadoxine-Pyrimethamine for the Chemoprevention of Malaria in Sickle Cell Anaemia (CHEMCHA)

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ClinicalTrials.gov Identifier: NCT04844099
Recruitment Status : Recruiting
First Posted : April 14, 2021
Last Update Posted : August 9, 2021
Sponsor:
Collaborators:
University of Bergen
University of Malawi
Makerere University
Indiana University
Global Health Uganda LTD
Information provided by (Responsible Party):
Liverpool School of Tropical Medicine

Study Description
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Brief Summary:

Sickle Cell Anaemia (SCA) is an inherited disease that makes the body produce red blood cells with abnormal sickle-shaped cells. The sickle-shaped cells are rigid, not flexible and break up easily resulting in anaemia. The abnormal cells also stick to the vessel walls, causing a blockage that slows or stops the flow of blood. When this happens, oxygen cannot reach nearby tissues. The lack of oxygen can cause attacks of sudden, severe pain, called pain crises, stroke or damage to important organs such as the spleen. All of these can lead to death. These attacks can occur without warning and are often started and made worse by infections such as malaria. Therefore, in many countries in Africa where malaria is common, children with SCA are given malaria medicines to prevent the infection. However, many of the medicines do not work effectively, are too difficult to take or they have side effects, resulting in poor adherence.

The aim of this study is to find safe, acceptable and effective medicines for malaria prevention in children with SCA in eastern and southern Africa. The investigators propose to conduct a study to find out whether giving weekly doses of dihydroartemisinin-piperaquine, also called DP, is safe, more effective, acceptable and cost-effective than the current strategy of monthly sulphadoxine-pyrimethamine (SP) to prevent malaria in children with sickle cell anaemia. Overall, 548 children aged 6 months to 15 years will be chosen randomly to receive either weekly DP or monthly SP for about 18 months. To test if the study medicine is effective, the study will compare the case burden of malaria. The investigators will also monitor every child for any type of illness, blood transfusions and other complications of sickle cell anaemia and admissions to the hospital. In addition, the study will evaluate the impact of DP on the development of resistance by malaria parasites. The study will also include nested safety studies on the effect of DP on the heart. All study participants will receive all the other usual care and treatments, including patient education on home care, and daily penicillin if younger than 5 years. If proven safe and efficacious, chemoprophylaxis with DP may decrease the incidence of malaria in children with SCA, prevent ill-health and deaths, and improve wellbeing.


Condition or disease Intervention/treatment Phase
Sickle Cell Anemia in Children Malaria Drug: Dihydroartemisinin Piperaquine Phase 2 Phase 3

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Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 548 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This will a randomised, double-blind, parallel-group superiority trial of weekly single day courses of DP for an average 18 months compared to monthly single-day courses of SP in SCA patients. The study will be conducted in Uganda and Malawi, using randomisation stratified by bodyweight and study centre. Participants will be randomised using an allocation of 1:1 to DP or SP. Patients on DP will also receive SP placebo, and those on SP will in addition, receive DP placebo
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: This will be a double-blinded study. Patients on DP will also receive SP placebo, and those on SP will in addition, receive DP placebo. All laboratory staff will be masked to the treatment assignment of individual participants. The trial statistician will also be blinded regarding the treatment code when he/she develops the statistical analysis plan and writes the statistical programmes, which will be validated and completed using dummy randomisation codes.
Primary Purpose: Prevention
Official Title: Dihydroartemisinin-Piperaquine or Sulphadoxine-Pyrimethamine for the Chemoprevention of Malaria in Children With Sickle Cell Anaemia in Eastern and Southern Africa: a Double Blind Randomised Trial (CHEMCHA)
Actual Study Start Date : April 9, 2021
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : June 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anemia Malaria

Arms and Interventions
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Arm Intervention/treatment
Experimental: Intervention arm
The intervention will be oral dihydroartemisinin (20mg) and piperaquine (160 mg) and administered once weekly at approximate doses of dihydroartemisinin 2.5mg/kg/day and piperaquine 20mg/kg/day based on participants' weight categories
 Drug: Dihydroartemisinin Piperaquine
Administered as dihydroartemisinin (20mg) and piperaquine (160 mg)
Other Name: D-ARTEPP® (Guilin Pharmaceutical Co. Ltd)
Active Comparator: Comparator
The active control will be Sulphadoxine-Pyrimethamine (SP), the current standard of care for malaria chemoprevention for SCA in Uganda and Malawi. This will also be provided by Guilin Pharmaceutical Co. Ltd as their generic World Health Organization-approved sulphadoxine-pyrimethamine 500/25mg tablets. It will be administered as monthly single-day courses of SP at approximate doses of S=25mg/kg and P=1.25mg/kg.
 Drug: Dihydroartemisinin Piperaquine
Administered as dihydroartemisinin (20mg) and piperaquine (160 mg)
Other Name: D-ARTEPP® (Guilin Pharmaceutical Co. Ltd)


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of clinical malaria [ Time Frame: 18 months ]
    An episode of malaria will be defined as a history of fever in the preceding 48hrs or documented axillary temperature ≥37.5 degrees centigrade plus microscopy confirmed Plasmodium falciparum malaria


Secondary Outcome Measures :
  1. All cause sick visits [ Time Frame: 18 months ]
    The incidence of all cause sick visits

  2. Incidence of malaria parasitaemia [ Time Frame: 18 months ]
    The incidence of malaria parasitaemia

  3. Malaria specific sick visits [ Time Frame: 18 months ]
    The incidence of malaria-specific sick visits

  4. All-cause and malaria-specific hospitalisation [ Time Frame: 18 months ]
    The incidence of all-cause and malaria-specific hospitalisation

  5. Sickle Cell Anaemia-related vaso-occlusive events [ Time Frame: 18 months ]
    The incidence of SCA-related vaso-occlusive events (including severe pain events and dactylitis); acute chest syndrome, stroke and need for blood transfusion

  6. Death [ Time Frame: 18 months ]
    The incidence of death.

  7. QTc prolongation [ Time Frame: 18 months ]
    Change in Corrected QT interval (QTc) length and QTc-prolongation on four-monthly ECG recordings.

  8. Serious cardiac adverse events [ Time Frame: 18 months ]
    Incidence of serious cardiac adverse events (e.g., convulsions or syncope within 48 hours after drug intake)

  9. Serious adverse events [ Time Frame: 18 months ]
    Incidence of serious adverse events

  10. Tolerance - vomiting [ Time Frame: 18 months ]
    1. Vomiting the study drug within 30 min of administration;
    2. Incidence of gastrointestinal complaints.

  11. Other gastro-intestinal complaints [ Time Frame: 18 months ]
    Incidence of gastrointestinal complaints.

  12. Level of adherence [ Time Frame: 18 months ]
    Level of adherence to study drugs

  13. Provider costs [ Time Frame: 18 months ]
    Provider costs of delivering the interventions and provider costs of managing malaria in SCA children.

  14. Direct and indirect costs [ Time Frame: 18 months ]
    Direct and indirect costs of patients receiving the interventions and managing cases of malaria.

  15. Incremental cost-effectiveness [ Time Frame: 18 months ]
    Incremental cost-effectiveness of replacing current standards of care (SP) with DP or DP+SP from the perspectives of the health care provider and the society.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   6 Months to 15 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  1. Children ages 6 months - 15 years
  2. Has a laboratory diagnosis of Sickle Cell Anaemia (HbSS) on haemoglobin electrophoresis, High-Performance Liquid Chromatography or Iso-electric focusing;
  3. Weighs ≥5kg;
  4. The parent has provided written consent.

Exclusion Criteria:

  1. Known chronic disease e.g. congenital heart disease;
  2. Known red cell disorder e.g. thalassaemia, glucose-6-phosphate dehydrogenase deficiency;
  3. Known allergy to DP or SP;
  4. Receiving daily cotrimoxazole prophylaxis;
  5. Unlikely to comply with the follow-up schedule;
  6. Participating in another trial
Contacts and Locations
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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): NCT04844099


Contacts
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Contact: Richard Idro, PhD +256 774274173 ridro1@gmail.com
Contact: Kamija Phiri, PhD +265 999 957 048; kamijaphiri@gmail.com

Locations
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Malawi
Queen Elizabeth Hospital Recruiting
Blantyre, Malawi
Contact: Nomsa Phiri, MBBS       nphirimd@gmail.com   
Uganda
Jinja Regional Referral hospital Recruiting
Jinja, Uganda
Contact: Pamela Akun, MA       pamakun@gmail.com   
Kitgum General Hospital Recruiting
Kitgum, Uganda
Contact: Pamela Akun, MA       pamakum@gmail.com   
Sponsors and Collaborators
Liverpool School of Tropical Medicine
University of Bergen
University of Malawi
Makerere University
Indiana University
Global Health Uganda LTD
Investigators
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Study Director: Robberstad Bjarne, PhD University of Bergen, Norway
More Information
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Publications:

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Responsible Party: Liverpool School of Tropical Medicine
ClinicalTrials.gov Identifier: NCT04844099    
Other Study ID Numbers: 19-105
First Posted: April 14, 2021    Key Record Dates
Last Update Posted: August 9, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: At the end of the study, anonymised data will be available to other researchers for further analysis,
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Beginning of 2025
Access Criteria:
  1. Ethical approval has been obtained.
  2. The terms of the original patient consent are not violated.
  3. The agreement on its use is according to prevailing laws on intellectual property rights.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Liverpool School of Tropical Medicine:
dihydroartemisinin-piperaquine
sulphadoxine pyrimethamine
sickle cell
 malaria
chemoprevention
prophylaxis
Additional relevant MeSH terms:
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Malaria
Anemia
Anemia, Sickle Cell
Hematologic Diseases
Protozoan Infections
Parasitic Diseases
Infections
Vector Borne Diseases
Anemia, Hemolytic, Congenital
 Anemia, Hemolytic
Hemoglobinopathies
Genetic Diseases, Inborn
Piperaquine
Artenimol
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents