Assessment of Artesunate/Mefloquine in the Peruvian Amazon

NCT02084602 | Completed Phase 4 DMC

• 1 other identifier: U.2012.0008
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

There is growing evidence of the emergence of P. falciparum resistance to artesunate (a derivative of artemisin) in Southeast Asia. The emergence and spread of resistant strains to artemisinin would represent an alarming threat to the success of the antimalarial combination therapy in the region. The delayed clearance of parasitemia for more than 24 hours has been taken as an early sign of resistance, a phenomenon seen at the Thai-Cambodia border. The purpose of this research study, is to assess the in vitro and in vivo efficacy of combinated artesunate/mefloquine therapy to treatment of uncomplicated Plasmodium falciparum malaria in the Peruvian Amazon through the analysis of the rate of clearance of parasitemia and other important outcomes.

Conditions

Malaria, Falciparum

Keywords

artesunate; mefloquine; falciparum; peruvian amazon

Outcome Measures

Primary Outcomes (1)

• Parasite clearance time

  Parasite clearance time assessed by microscopy and quantitative PCR

  up to 72 hours after administration of artesunate

Secondary Outcomes (4)

• Parasite reduction rates and ratios

  24, 48 hours after the first administration of artesunate

• Time for parasite count to fall

  at least 24 hours

• Fever clearance time

  at least 24 hours

• Gametocyte carriage rates

  up to 14 days since the first administration of artesunate

Study Arms (1)

Artesunate/mefloquine

EXPERIMENTAL

Orally administration of artesunate 4mg/Kg by three days Orally administration of mefloquine 15mg/Kg in the fourth day Orally administration of mefloquine 10mg/Kg in the fifth day

Drug: Artesunate; Drug: Mefloquine

Interventions

Artesunate DRUG

Orally administration of artesunate 4mg/Kg by three days

Also known as: Distribuited by AC Farma

Artesunate/mefloquine

Mefloquine DRUG

Orally administration of mefloquine 15mg/Kg in the fourth day Orally administration of mefloquine 10mg/Kg in the fifth day

Also known as: Distribuited by AC Farma

Artesunate/mefloquine

Eligibility Criteria

• Age: 5 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 5 and 65 years old inclusive
• Monoinfection of P. falciparum confirmed by microscopy
• Documented fever (axillary temperature \> 37.5°C) and/or history of fever during the previous 48 hours in the absence of other obvious causes of fever (such as pneumonia, otitis media, etc)
• Infection with P. falciparum of 1000 and 100,000 asexual parasites per microliter (μl) to be determined by microscopic examination of a thick or thin smear, and positive confirmation by polymerase chain reaction (PCR); \* Presence of sexual form of P. vivax is acceptable; \*\* PCR confirmation is not an enrollment requirement
• Informed consent must be obtained from the participant or both parents/guardian (in the case of children), and assent from the child (from 8 to 17 years old)
• Willingness of the participant to return to the health facility for regular check-ups during the follow-up period of 42 days
• Willingness of the participant to transfer to the Hospital de Apoyo Iquitos to start treatment

You may not qualify if:

• Severe malaria signs (as defined by the World Health Organization):
• Cerebral malaria (irreversible coma)
• Severe anemia (hematocrit \< 15%, or clinic signs)
• Clinic signs of kidney failure (e.g., serum creatinine \> 3 mg/dL)
• Pulmonary edema
• Hypoglycemia (glucose in the blood \<40mg/dL or clinic signs)
• Shock (PA systolic \< 70 mm Hg in adults; \< 50 in children)
• Spontaneous bleeding/Disseminated intravascular coagulation (CID)
• Recurrent generalized convulsions
• Acidemia/acidosis (clinic signs)
• Macroscopic hemoglobinuria
• Jaundice Laboratory tests for measuring some of these conditions may not be available at all study sites. If they are not, we will use clinical criteria of severe malaria at the discretion of the study physician
• Background of other chronic or severe diseases (e.g., heart, kidney, liver diseases, HIV/AIDS, severe malnutrition), determined clinically by medical history and physical examination
• Background of hypersensitivity to any of the drugs tested or used as an alternative treatment: AS, MQ, quinine or tetracycline/clindamycin
• Gestation (based on a serum pregnancy test or medical history) or desire to become pregnant during the study period, or not using any family planning method while being sexually active (confirmed by urine pregnancy test)

Sponsors & Collaborators

• Instituto Nacional de Salud. Peru: lead
• U.S. Naval Medical Research Unit No.6 (NAMRU-6): collaborator

Study Sites (1)

NAMRU 6

Iquitos, Loreto, 5116, Peru

Location

Related Publications (5)

• Durand S, Sihuincha M, Lachira A, Chaves J, Cabezas C. [A need to monitor P. falciparum resistance to artesunate in Peru]. Rev Peru Med Exp Salud Publica. 2012 Oct-Dec;29(4):579-80. doi: 10.1590/s1726-46342012000400028. No abstract available. Spanish.

  PMID: 23338651 BACKGROUND

• de Oliveira AM, Chavez J, de Leon GP, Durand S, Arrospide N, Roberts J, Cabezas C, Marquino W. Efficacy and effectiveness of mefloquine and artesunate combination therapy for uncomplicated Plasmodium falciparum malaria in the Peruvian Amazon. Am J Trop Med Hyg. 2011 Sep;85(3):573-8. doi: 10.4269/ajtmh.2011.11-0250.

  PMID: 21896825 BACKGROUND

• Gutman J, Green M, Durand S, Rojas OV, Ganguly B, Quezada WM, Utz GC, Slutsker L, Ruebush TK 2nd, Bacon DJ. Mefloquine pharmacokinetics and mefloquine-artesunate effectiveness in Peruvian patients with uncomplicated Plasmodium falciparum malaria. Malar J. 2009 Apr 9;8:58. doi: 10.1186/1475-2875-8-58.

  PMID: 19358697 BACKGROUND

• Alker AP, Lim P, Sem R, Shah NK, Yi P, Bouth DM, Tsuyuoka R, Maguire JD, Fandeur T, Ariey F, Wongsrichanalai C, Meshnick SR. Pfmdr1 and in vivo resistance to artesunate-mefloquine in falciparum malaria on the Cambodian-Thai border. Am J Trop Med Hyg. 2007 Apr;76(4):641-7.

  PMID: 17426163 BACKGROUND

• Wongsrichanalai C, Meshnick SR. Declining artesunate-mefloquine efficacy against falciparum malaria on the Cambodia-Thailand border. Emerg Infect Dis. 2008 May;14(5):716-9. doi: 10.3201/eid1405.071601.

  PMID: 18439351 BACKGROUND

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Artesunate; Mefloquine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Salomon Durand, Master

  NAMRU 6

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 7, 2014
• First Posted: March 12, 2014
• Study Start: June 18, 2014
• Primary Completion: November 6, 2015
• Study Completion: April 13, 2016
• Last Updated: April 29, 2021

Record last verified: 2021-04

Locations

PE (1)