NCT01958905

Brief Summary

The general objective of the study is to answer to the question: "Is the current dose of AL less efficacious in the severely malnourished compared to the non-severely malnourished children, and is PK in cause?" We aim to assess whether the current treatment dose is adequate for children with severe acute malnutrition, and we hope results will guide further recommendations for malaria treatment in this specific population.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
399

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Nov 2013

Geographic Reach
2 countries

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 7, 2013

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 9, 2013

Completed
23 days until next milestone

Study Start

First participant enrolled

November 1, 2013

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2015

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2015

Completed
Last Updated

December 18, 2015

Status Verified

December 1, 2015

Enrollment Period

1.3 years

First QC Date

October 7, 2013

Last Update Submit

December 17, 2015

Conditions

MalariaSevere Acute Malnutrition

Outcome Measures

Primary Outcomes (1)

  • Proportion of adequate clinical and parasitological response after PCR correction

    Standard primary outcome as defined wy the WHO guidelines for assessing antimalarial efficacy

    28 days

Secondary Outcomes (5)

  • Percentage of adequate clinical and parasitological response corrected by PCR

    42 days

  • Proportion of treatment failures by types (Early Treatment Failure, Late Clinical Failure, Late Parasitological Failure)

    28 and 42 days

  • Proportion of reinfection and recrudescence

    28 and 42 days

  • Bio-availability of lumefantrine

    21 days

  • Type and frequency of adverse events

    42 days

Other Outcomes (1)

  • Level of antimalarial antibodies at enrolment

    Enrolment

Study Arms (1)

Artemether-Lumefantrine

EXPERIMENTAL

All patients will receive Artemether-Lumefantrine and the endpoints will be compared between the two populations of severely malnourished and non-severely malnourished children

Drug: Artemether-lumefantrine fixed combination

Interventions

Artemether-lumefantrine fixed combinationDRUG
Also known as: Coartem Novartis
Artemether-Lumefantrine

Eligibility Criteria

Age6 Months - 5 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Age between 6 and 59 months
  • Weight ≥ 5 kg
  • P. falciparum monoinfection confirmed on a thick blood film
  • Parasitic density between 1,000 and 200,000 asexual forms/µL of blood.
  • Measured axillary temperature ≥ 37.5 ° C or history of fever during the previous 24 hours
  • High probability of compliance with follow-up visits (no near-term travel plans)
  • Consent of a parent or guardian who is at least 18 years of age.
  • According to the group: in severely malnourished, weight-for-height z-score \<-3 SD or MUAC \<115 mm, and in non-severely malnourished, weight-for-height z-score ≥- 3 standard deviations (SD), and MUAC≥ 115 mm.

You may not qualify if:

  • General danger signs or signs of complicated malaria as defined by the WHO (Appendix 1)
  • Mixed or mono-infection with another Plasmodium species detected by microscopy
  • Severe anemia (hemoglobin \<5 g / dL)
  • Known underlying chronic or severe disease (e.g. cardiac, renal or hepatic disease, tuberculosis, sickle cell)
  • Known HIV/AIDS infection
  • Known history of hypersensitivity or contra-indication to any of the study medications: artemether, lumefantrine (first-line medications), or artesunate, amodiaquine (rescue medications)
  • Presence of febrile conditions due to diseases other than malaria which could alter the outcome of the study
  • History of a full treatment course with AL in the past 14 days.
  • Height-for-age \<-3 Z scores
  • Severe complications of malnutrition requiring hospitalization in intensive care or stabilization: Severe signs of kwashiorkor, Anorexia (failure to the appetite test), Hyperemesis, Severe acute infection, Hypothermia \<35 ˚ C (axillary) or hypoglycemia, Diarrhea with dehydration, Lethargy, coma, Clinical signs of vitamin A deficiency (xerophthalmia)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

District Hospital

Wolossébougou, Mali

Location

CSI Andoumè

Maradi, Niger

Location

Related Publications (3)

  • Chotsiri P, Denoeud-Ndam L, Baudin E, Guindo O, Diawara H, Attaher O, Smit M, Guerin PJ, Doumbo OK, Wiesner L, Barnes KI, Hoglund RM, Dicko A, Etard JF, Tarning J. Severe Acute Malnutrition Results in Lower Lumefantrine Exposure in Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria. Clin Pharmacol Ther. 2019 Dec;106(6):1299-1309. doi: 10.1002/cpt.1531. Epub 2019 Jul 23.

    PMID: 31152555DERIVED

  • Denoeud-Ndam L, Dicko A, Baudin E, Guindo O, Grandesso F, Diawara H, Sissoko S, Sanogo K, Traore S, Keita S, Barry A, de Smet M, Lasry E, Smit M, Wiesner L, Barnes KI, Djimde AA, Guerin PJ, Grais RF, Doumbo OK, Etard JF. Efficacy of artemether-lumefantrine in relation to drug exposure in children with and without severe acute malnutrition: an open comparative intervention study in Mali and Niger. BMC Med. 2016 Oct 24;14(1):167. doi: 10.1186/s12916-016-0716-1.

    PMID: 27776521DERIVED

  • Denoeud-Ndam L, Dicko A, Baudin E, Guindo O, Grandesso F, Sagara I, Lasry E, Palma PP, Parra AM, Stepniewska K, Djimde AA, Barnes KI, Doumbo OK, Etard JF. A multi-center, open-label trial to compare the efficacy and pharmacokinetics of Artemether-Lumefantrine in children with severe acute malnutrition versus children without severe acute malnutrition: study protocol for the MAL-NUT study. BMC Infect Dis. 2015 Jun 12;15:228. doi: 10.1186/s12879-015-0963-3.

    PMID: 26068100DERIVED

MeSH Terms

Conditions

MalariaSevere Acute Malnutrition

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne DiseasesMalnutritionNutrition DisordersNutritional and Metabolic Diseases

Study Officials

  • Jean-Francois Etard, MD, PHD

    Epicentre

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 7, 2013

First Posted

October 9, 2013

Study Start

November 1, 2013

Primary Completion

March 1, 2015

Study Completion

May 1, 2015

Last Updated

December 18, 2015

Record last verified: 2015-12

Locations

NI(1)MA(1)