Assessment of the Therapeutic Efficacy and Tolerability of the Artesunate/Amodiaquina Combination and Artemether/Lumefantrine Combination, Treatment of Uncomplicated P. Falciparum Malaria in the Department of Chocó (Colombia)

NCT04877626 | Completed Phase 4 DMC

• 1 other identifier: Treatment malaria in Colombia
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Malaria by P falciparum is a public health problem in more than 100 municipalities of Colombia. The country is using the artemether+lumefantrine (AM+L) fixed combination for uncomplicated P falciparum malaria but it is ideal to have different types of formulations with similar efficacy that may be used in diverse circumstances. One alternative of treatment is using preparations containing artesunate and amodiaquine (AS+AQ) in fixed combination, which can be given in a simpler dosing regimen. In order to assess the efficacy of that combination in an area with suspected risk of resistance to amodiaquine an open controlled clinical trial was carried out in Colombia. Methods: The study was done in Choco, a high endemic area for malaria by P falciparum, from August 2008 and September 2009. Patients diagnosed with uncomplicated malaria (n=210) malaria were randomized in two arms, one receiving AS+AQ and the other AM+L. The main clinical results was parasitological cure, i.e. a negative blood smears, that was assessed, for both groups, at days 1, 2, 3, 7, 14, 21 and 28 after the onset of treatment. Results: There were no losses at follow up. The mean age of the enrolled study subjects was of 37.5 years without differences between study arms. Both therapies were very well tolerated in general. The efficacy for AS+AQ was 100%, and 99% for AM+L (p\>0.1). In average, patients in the AS+AQ arm became negative for P falciparum parasites and gametocytes earlier than those at the AM+L arm. Blood smears became negative after one day of treatment with AS+AQ and after two days of treatment with AM+L. Gametocytes disappeared after 2 days of treatment in the AS+AQ arm compared to 4 days in the AM+L arm. Conclusions: In this study, the efficacy of the AS+AQ combination was similar to that of the AM+L. This finding do not support the hypothesis that there is a level of resistance to amodiaquine that prevents its use combined with artemisinin derived.

Conditions

P. Falciparum Malaria

Keywords

uncomplicated P. falciparum malaria; Colombia

Outcome Measures

Primary Outcomes (1)

• The primary efficacy endpoint was the adequate clinical and parasitological response (ACPR)

  Absence of parasitemia on day 28, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure

  28 days

Study Arms (2)

AQ+AS

ACTIVE COMPARATOR

Group 1 received the combination AQ+AS (COARSUCAM®) which was administered orally at an initial dose of 2 tablets (200 mg AQ/540 mg AS) followed by 2 additional doses of 2 tablets at 24 and 48 hours (6 tablets in 48 hours).

Drug: Artemeter plus lumefantrina vs artesunato plus amodiquina

AM+L

ACTIVE COMPARATOR

Group 2 received the combination Artemeter+lumefantrina (COARTEM®) administered orally at an initial dose of 4 tablets (80 mg artemeter/480 mg lumefantrina) followed by 5 additional doses of 4 tablets at 8, 24, 36, 48, and 60 hours (24 tablets in 60 hours)

Drug: Artemeter plus lumefantrina vs artesunato plus amodiquina

Interventions

Artemeter plus lumefantrina vs artesunato plus amodiquina DRUG

Group 1 received the combination AQ+AS (COARSUCAM®) which was administered orally at an initial dose of 2 tablets (200 mg AQ/540 mg AS) followed by 2 additional doses of 2 tablets at 24 and 48 hours (6 tablets in 48 hours). Group 2 received the combination Artemeter+lumefantrina (COARTEM®) administered orally at an initial dose of 4 tablets (80 mg artemeter/480 mg lumefantrina) followed by 5 additional doses of 4 tablets at 8, 24, 36, 48, and 60 hours (24 tablets in 60 hours)

AM+L; AQ+AS

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years
• fever (axillary temperature \>37.5º C) or history of fever during the prior 48 hours in absence of another obvious cause (such as pneumonia, otitis media)
• a non-mixed P. falciparum infection with 250 and 100,000 asexual parasites/µl to be determined by a thick film or thick film and blood smear microscopic test

You may not qualify if:

• Not being able to drink
• vomiting (more than twice within the prior 24 hours)
• recent history of seizures (1 or more in the previous 24 hours)
• alteration of the consciousness level
• not being able to seat or stand up, signs of serious malaria (World Health Organization criteria)
• other chronic or severe diseases (i.e., cardiac, renal and hepatic diseases, HIV/AIDS, severe malnutrition)
• history of hypersensibility to any of the study drugs or drugs used as alternative treatment (i.e. mefloquine, artesunate, quinine or tetracycline/clindamycin)
• suspicion of pregnancy or pregnancy (based on a urine pregnancy test).

Sponsors & Collaborators

• Universidad Nacional de Colombia: lead
• Sanofi Pasteur, a Sanofi Company: collaborator

Study Sites (1)

San Rafael Hospital in Quibdó Chocó

Quibdó, Departamento del Chocó, 57, Colombia

Location

Study Officials

• Alejandro AR Rico, Epidemiologist

  Universidad Nacional de Colombia

  STUDY CHAIR

• Fernando FH De la Hoz, PhD

  Universidad Nacional de Colombia

  PRINCIPAL INVESTIGATOR

• Alexandra AP Porras, Epidemiologist

  Universidad Nacional de Colombia

  STUDY DIRECTOR

• Freddy FC Cordoba, Epidemiologist

  Chocó

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2010
• First Posted: May 7, 2021
• Study Start: September 1, 2008
• Primary Completion: October 1, 2009
• Study Completion: December 1, 2009
• Last Updated: May 7, 2021

Record last verified: 2021-05

Locations

CO (1)