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

NCT04844099 | Completed Phase 3 DMC

• 1 other identifier: 19-105
• Study Type: interventional
• Target: 723
• Locations: 2 countries
• Sites: 3

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.

Conditions

Sickle Cell Anemia in Children; Malaria

Keywords

dihydroartemisinin-piperaquine; sulphadoxine pyrimethamine; sickle cell; malaria; chemoprevention; prophylaxis

Outcome Measures

Primary Outcomes (1)

• Incidence of clinical malaria

  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

  18 months

Secondary Outcomes (15)

• All cause sick visits

  18 months

• Incidence of malaria parasitaemia

  18 months

• Malaria specific sick visits

  18 months

• All-cause and malaria-specific hospitalisation

  18 months

• Sickle Cell Anaemia-related vaso-occlusive events

  18 months

Study Arms (2)

Intervention arm

EXPERIMENTAL

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

Comparator

ACTIVE 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

Interventions

Dihydroartemisinin Piperaquine DRUG

Administered as dihydroartemisinin (20mg) and piperaquine (160 mg)

Also known as: D-ARTEPP® (Guilin Pharmaceutical Co. Ltd)

Comparator; Intervention arm

Eligibility Criteria

• Age: 6 Months - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• Known chronic disease e.g. congenital heart disease;
• Known red cell disorder e.g. thalassaemia, glucose-6-phosphate dehydrogenase deficiency;
• Known allergy to DP or SP;
• Receiving daily cotrimoxazole prophylaxis;
• Unlikely to comply with the follow-up schedule;
• Participating in another trial

Sponsors & Collaborators

• Liverpool School of Tropical Medicine: lead
• University of Bergen: collaborator
• University of Malawi: collaborator
• Makerere University: collaborator
• Indiana University: collaborator
• Global Health Uganda LTD: collaborator

Study Sites (3)

Queen Elizabeth Hospital

Blantyre, Malawi

Location

Jinja Regional Referral hospital

Jinja, Uganda

Location

Kitgum General Hospital

Kitgum, Uganda

Location

Related Publications (25)

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MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Robberstad Bjarne, PhD

  University of Bergen, Norway

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This will be a randomized, double-blind, parallel-group superiority trial of weekly single-day courses of DP for an average of 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 randomized using an allocation of 1:1 to DP or SP. Patients on DP will also receive an SP placebo, and those on SP will in addition, receive a DP placebo

Study Record Dates

• First Submitted: March 26, 2021
• First Posted: April 14, 2021
• Study Start: April 9, 2021
• Primary Completion: June 30, 2023
• Study Completion: July 12, 2023
• Last Updated: September 13, 2023

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

MA (1); UG (2)