NCT01374581

Brief Summary

This is a bi-centric phase IIIb, randomized, open label, 3-arm clinical trial performed to investigate the impact of retreatment with an Artemisinin-Based Combination (ACT), for example Arthemeter-Lumefantrine (AL) in Uganda (Ug) and artesunate-amodiaquine (ASAQ) in RDCongo, on malaria incidence and its potential selection of resistant strains. Patients will be followed-up for efficacy and safety during 42 days after treatment with the first line therapy recommended by the national authorities(arthemeter-lumefantrine in Uganda and artesunate-amodiaquine in RDCongo) and retreated the patients either with the same ACT or an other ACT or oral Quinine + clyndamicin. The investigators hypothesize that (re)treatment with the first line ACT treatment beyond 14 days is as efficacious as any other rescue treatment, without the risk of selecting drug resistant strains.

Trial Health

90
On Track

Trial Health Score

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

Enrollment
2,117

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started May 2012

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

June 9, 2011

Completed
7 days until next milestone

First Posted

Study publicly available on registry

June 16, 2011

Completed
11 months until next milestone

Study Start

First participant enrolled

May 1, 2012

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2014

Completed
Last Updated

October 22, 2014

Status Verified

October 1, 2014

Enrollment Period

2.1 years

First QC Date

June 9, 2011

Last Update Submit

October 21, 2014

Conditions

Keywords

retreatmentartemisinin-based combinationmalariaresistant

Outcome Measures

Primary Outcomes (1)

  • Late Parasitological Failure

    Parasitaemia after day 3 in the absence of fever (axillary temperature \<37.5°C)

    Day4-Day28

Secondary Outcomes (7)

  • PCR unadjusted efficacy

    Day 28 days

  • Day 42 clinical efficacy

    Day 42

  • Change in Fever clearance time (FCT)

    Day 0, Day 1, Day 2

  • Change in Asexual parasite clearance time

    Day 0, Day 1, Day 2

  • Hb changes

    Day 0, Days 14 and Day 28

  • +2 more secondary outcomes

Study Arms (3)

Artemether/Lumefantrine

EXPERIMENTAL

Tablets 20 mg/120 of Artemether/Lumefantrine will be given to 124 trial patients

Drug: Artemether/Lumefantrine

Artesunate/Amodiaquine

EXPERIMENTAL

Tablets 25mg/67,5 mg of Artesunate/Amodiaquine will be given to 124 trial patients.

Drug: Artesunate/Amodiaquine

Quinine + Clindamycin

ACTIVE COMPARATOR

Quinine tablet 125mg + Clindamycin syrup 75mg/5ml will be given to 60 children.

Drug: Quinine + Clindamycin

Interventions

Tablets containing 20 mg of Artemether and 120 mg of Lumefantrine. Each dose to be taken with high-fat food or drinks (for example milk). Weight in kg Number of tablet per dose Age 5 to \< 15 kg 1 tablet per dose 15 to \< 25 kg 2 tablets per dose 25 to \< 35 kg 3 tablets per dose

Also known as: Coartem®
Artemether/Lumefantrine

Age (Weight in Kg) Dose Treatment duration 2 to 11 months (= 4,5 to \< 9kg):1 tablet (25 mg/675mg) for 3 days 1 to 5 years (= 9 kg to \< 18 kg)1 tablet(25mg/67,5mg)for 3 days

Also known as: Co-arsucam®
Artesunate/Amodiaquine

this arm consist to 7 days treatment of 60 patients with quinine tablet 125mg + clindamycin syrup as follow; Quinine: 9 to \< 11 kg: ½ tablets 12 to \< 19 kg: 1 tablets per dose 20 to \< 27 kg: 1½ tablets per dose 28 to \< 35 kg: 2 tablets per dose Clindamycin syrup: 10 mg/kg twice daily

Also known as: Quinimax® tablet 125mg, Dalacin® syrup 75mg/5ml
Quinine + Clindamycin

Eligibility Criteria

Age12 Months - 59 Months
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Have been enrolled in the first phase
  • Recurrent Plasmodium falciparum infection with clinical symptoms.
  • Parents' or guardians' willingness and ability to comply with the study protocol for the duration of the study.
  • Signed (or thumb-printed whenever parents/guardians are illiterate) (second) informed consent by the parents or guardians. Note: the informed consent will cover the whole period of the study, including additional active follow ups

You may not qualify if:

  • Patients with at least one of the following criteria will be excluded:
  • Participation in any other investigational drug study (antimalarial or others) during the previous 30 days.
  • Known hypersensitivity and previous Serious Adverse Events related to the study drugsto the study drugs.
  • Severe malaria( WHO 2000) or danger signs: not able to drink or breast-feed, vomiting (\> twice in 24hours), recent history of convulsions (\>1 in 24h), unconscious state, unable to sit or stand.
  • Presence of intercurrent illness or any condition (cardiac, renal, hematologic, hepatic diseases) which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study, including known G6PD deficiency.
  • Patients who are taking drug which may prolong the QT (imidazole and triazole, antifungal agent).
  • Severe malnutrition (defined as weight for height \<70% of the median NCHS/WHO reference).
  • Ongoing prophylaxis with drugs having antimalarial activity such as cotrimoxazole for the prevention of Pneumocisti carini pneumonia in children born to HIV+ women.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Centre de Santé Lisungi

Kinshasa, Mont-Ngafula, Route Kimwenza n°23, Republic of the Congo

Location

Kazo Health centre IV

Kiruhura, P.O Box 5 Rushere, Uganda

Location

Related Publications (3)

  • Mavoko HM, Nabasumba C, da Luz RI, Tinto H, D'Alessandro U, Kambugu A, Baraka V, Rosanas-Urgell A, Lutumba P, Van Geertruyden JP. Efficacy and safety of re-treatment with the same artemisinin-based combination treatment (ACT) compared with an alternative ACT and quinine plus clindamycin after failure of first-line recommended ACT (QUINACT): a bicentre, open-label, phase 3, randomised controlled trial. Lancet Glob Health. 2017 Jan;5(1):e60-e68. doi: 10.1016/S2214-109X(16)30236-4. Epub 2016 Nov 11.

  • Muhindo Mavoko H, Kalabuanga M, Delgado-Ratto C, Maketa V, Mukele R, Fungula B, Inocencio da Luz R, Rosanas-Urgell A, Lutumba P, Van Geertruyden JP. Uncomplicated Clinical Malaria Features, the Efficacy of Artesunate-Amodiaquine and Their Relation with Multiplicity of Infection in the Democratic Republic of Congo. PLoS One. 2016 Jun 9;11(6):e0157074. doi: 10.1371/journal.pone.0157074. eCollection 2016.

  • Muhindo Mavoko H, Nabasumba C, Tinto H, D'Alessandro U, Grobusch MP, Lutumba P, Van Geertruyden JP. Impact of retreatment with an artemisinin-based combination on malaria incidence and its potential selection of resistant strains: study protocol for a randomized controlled clinical trial. Trials. 2013 Sep 23;14:307. doi: 10.1186/1745-6215-14-307.

MeSH Terms

Conditions

Malaria

Interventions

Artemether, Lumefantrine Drug Combinationamodiaquine, artesunate drug combinationQuinineClindamycin

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Intervention Hierarchy (Ancestors)

ArtemetherArtemisininsReactive Oxygen SpeciesFree RadicalsInorganic ChemicalsOrganic ChemicalsLumefantrineFluorenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSesquiterpenesTerpenesPolycyclic CompoundsDrug CombinationsPharmaceutical PreparationsCinchona AlkaloidsAlkaloidsHeterocyclic CompoundsQuinuclidinesHeterocyclic Compounds, Bridged-RingQuinolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingLincomycinLincosamidesPyrrolidinesHeterocyclic Compounds, 1-RingGlycosidesCarbohydrates

Study Officials

  • Hypolite M. Mavoko, MD MPH

    Kinshasa University, RDCongo

    PRINCIPAL INVESTIGATOR
  • Carolyn Nabasumba, M.B.Ch.B

    Kazo health centre IV Uganda

    PRINCIPAL INVESTIGATOR
  • Jean-Pierre Van geertruyden, MD MPH PhD

    International Health Unit Antwerp university

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Prof

Study Record Dates

First Submitted

June 9, 2011

First Posted

June 16, 2011

Study Start

May 1, 2012

Primary Completion

June 1, 2014

Study Completion

June 1, 2014

Last Updated

October 22, 2014

Record last verified: 2014-10

Locations