Efficacy and Safety of Artesunate + Amodiaquine With SLD of Primaquine for Treatment of Falciparum Malaria in Zanzibar

NCT03773536 | Completed Phase 4

• 1 other identifier: Aco V
• Study Type: interventional
• Target: 146
• Locations: 1 country
• Sites: 1

Brief Summary

The general objective of this study is to assess the therapeutic efficacy and safety of artesunate + amodiaquine combined with a single low dose of primaquine (0.25 mg/kg) for the treatment of uncomplicated P. falciparum malaria patients in Zanzibar. The specific objectives are:

• To determine the clinical and parasitological efficacy of artesunate + amodiaquine and primaquine in the treatment of uncomplicated Plasmodium falciparum infection.
• To differentiate recurrent infections during follow-up, i.e. recrudescence from new infections, by polymerase chain reaction (PCR).
• To evaluate the incidence of adverse events, particularly with regards to potential hematological adverse events of primaquine.
• To determine the polymorphism of molecular markers associated with artesunate + amodiaquine tolerance/resistance.
• To formulate recommendations, which will enable the Zanzibar Ministry of Health to make informed decisions about whether the current national antimalarial treatment guidelines should be updated or not.
• To determine efficacy rate of the first line treatment compared to the first efficacy trial thirteen years ago.

Conditions

Plasmodium Falciparum Malaria

Keywords

Artesunate-amodiaquine; Single Low Dose Primaquine; Zanzibar

Outcome Measures

Primary Outcomes (1)

• PCR corrected cure rates for assessing efficacy of artesunate + amodiaquine given together with a single low dose primaquine in the treatment of uncomplicated Plasmodium falciparum infection

  PCR corrected cure rates were to be assessed by genotype analysis of the following P. falciparum genes: the merozoite surface protein 1 (msp1) and 2 (msp2), and the glutamine-rich protein (glurp) (WHO 2008). The genotypic profiles of pre- and post-parasite strains were to be compared in a stepwise manner to distinguish recrudescence from reinfection.

  42 days

Secondary Outcomes (1)

• Safety of artesunate + amodiaquine and primaquine: Incidence of adverse events

  42 days

Other Outcomes (1)

• Monitoring molecular markers of drug resistance

  42 days

Study Arms (1)

ASAQ + SLD Primaquine

EXPERIMENTAL

Artesunate + amodiaquine (WHO prequalified Artesunate/Amodiaquine Winthrop®) was administered orally as a fixed dose combination, at a dose of approximately artesunate 4 mg/kg + amodiaquine 10mg/kg once daily for 3 consecutive days. Primaquine was administered orally, as a single dose (0.25 mg/kg) together with the first artesunate + amodiaquine dose. All doses of medicine were administered under direct supervision. Any patient who vomited within a 30 minute observation period was re-treated with the same dose of medicine and observed for an additional 30 minutes. If the patient vomited again after the second study drug administration, he/she was withdrawn and offered rescue therapy (Artesunate IV).

Drug: Artesunate-amodiaquine given with single low dose primaquine

Interventions

Artesunate-amodiaquine given with single low dose primaquine DRUG

Three day treatment with ASAQ with SLD primaquine given with the first dose of ASAQ.

ASAQ + SLD Primaquine

Eligibility Criteria

• Age: 3 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 3 months and above;
• P. falciparum infection detected by malaria rapid diagnostic test (mRDT) and confirmed by microscopy;
• Presence of P. falciparum malaria asexual parasitaemia (any level);
• Presence of axillary ≥37.5 °C or history of fever during the past 48 hours
• Ability to swallow oral medication;
• Ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule; and
• Informed consent from the patient or from a parent or guardian in the case of children.

You may not qualify if:

• Presence of general danger signs in children aged under 5 years or signs of severe falciparum malaria according to the definitions of WHO (Appendix 1);
• Mono-infection with a Plasmodium species other than P. falciparum detected by microscopy;
• Presence of febrile conditions other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. severe malnutrition, cardiac, renal and hepatic diseases, HIV/AIDS);
• Regular medication, which may interfere with the study drugs;
• History of hypersensitivity reactions or contraindications to any of the study medicines; and
• Pregnancy

Sponsors & Collaborators

• Professor Anders Björkman: lead
• Ministry of Health and Social Welfare, Zanzibar: collaborator
• Zanzibar Malaria Elimination Programme: collaborator
• Uppsala University: collaborator

Study Sites (1)

Micheweni, Bububu Jesheni, and Uzini

Zanzibar, Tanzania

Location

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Single Person; Primaquine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Marital Status; Family Characteristics; Demography; Population Characteristics; Socioeconomic Factors; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Mwinyi I Msellem

  Mnazi mmoja hospital, Zanzibar Ministry of Health

  PRINCIPAL INVESTIGATOR

• Abduallah S Ali

  Zanzibar Malaria Elimination Programme

  STUDY DIRECTOR

• Andreas Martensson

  Uppsala University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: A one-armed prospective antimalarial drug efficacy trial.

Study Record Dates

• First Submitted: December 3, 2018
• First Posted: December 12, 2018
• Study Start: May 9, 2017
• Primary Completion: September 25, 2017
• Study Completion: September 25, 2017
• Last Updated: December 12, 2018

Record last verified: 2018-12

Locations

TA (1)