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Impact of Artemisinin-based Combination Therapy and Quinine on Treatment Failure and Resistance in Uncomplicated Malaria (QuinAct)

This study is currently recruiting participants.
Verified January 2013 by Universiteit Antwerpen
Sponsor:
Collaborators:
European and Developing Countries Clinical Trials Partnership (EDCTP)
Fund for Scientific Research, Flanders, Belgium
Institute of Tropical Medicine, Belgium
University of Kinshasa
Centre Muraz
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Makerere University
Information provided by (Responsible Party):
Jean-Pierre Van geertruyden, Universiteit Antwerpen
ClinicalTrials.gov Identifier:
NCT01374581
First received: June 9, 2011
Last updated: January 15, 2013
Last verified: January 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Malaria
 Drug: Artemether/Lumefantrine
Drug: Artesunate/Amodiaquine
Drug: Quinine + Clindamycin
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Clinical Trial to Measure the Impact of Retreatment With an Artemisinin-based Combination on Malaria Incidence and Its Potential Selection of Resistant Strains

Resource links provided by NLM:

MedlinePlus related topics: Malaria
U.S. FDA Resources

Further study details as provided by Universiteit Antwerpen:

Primary Outcome Measures:
  • Late Parasitological Failure [ Time Frame: Day4-Day28 ] [ Designated as safety issue: No ]
    Parasitaemia after day 3 in the absence of fever (axillary temperature <37.5°C)


Secondary Outcome Measures:
  • PCR unadjusted efficacy [ Time Frame: Day 28 days ] [ Designated as safety issue: No ]
    Proportion of children without (PCR not adjusted) treatment failure (TF28U): all treatment failures detected during the active follow up, regardless of genotyping.

  • Day 42 clinical efficacy [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
    All clinical treatment failures detected during the 42 days follow up for the first line treatment, with and without PCR adjustment. As no active monitoring of parasitaemia after day 3 is planned this includes ETF and LCF following WHO criteria.

  • Change in Fever clearance time (FCT) [ Time Frame: Day 0, Day 1, Day 2 ] [ Designated as safety issue: No ]
    The time (in days) from the time of randomization to the first two consecutive measurements on 2 different days of axillary temperature below 37.5°C.

  • Change in Asexual parasite clearance time [ Time Frame: Day 0, Day 1, Day 2 ] [ Designated as safety issue: No ]

    Asexual parasite clearance time is defined as the time (in days) from time of randomization to 2 consecutive negative blood slides (collected at different days). The time to the event will be taken as the time to the first negative slide.

    5. Gametocytaemia (prevalence and density) at day 7, 14, 21 and 28 after treatment.


  • Hb changes [ Time Frame: Day 0, Days 14 and Day 28 ] [ Designated as safety issue: Yes ]
    Variation in Hb level between two measurements.

  • Early Treatment Failure [ Time Frame: Day0-Day3 ] [ Designated as safety issue: No ]
    Development of danger signs or severe malaria on Day 0, Day 1 Day 2 or Day 3, in the presence of parasitaemia Parasite density on Day 2 > Day 0 count, irrespective of axillary temperature Presence of parasitaemia on Day 3 with fever (axillary temperature ≥ 37.5°C) Parasitaemia on Day 3 ≥ 25 % of count on Day 0.

  • Late Clincial Failure [ Time Frame: Day0-Day28 ] [ Designated as safety issue: No ]
    Development of danger signs or severe malaria after Day 3 in the presence of parasitaemia Presence of parasitaemia and fever on any day from Day 4 to Day 28


Estimated Enrollment: 3600
Study Start Date: May 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Artemether/Lumefantrine
Tablets 20 mg/120 of Artemether/Lumefantrine will be given to 124 trial patients
 Drug: Artemether/Lumefantrine

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

Other Name: Coartem®
Experimental: Artesunate/Amodiaquine
Tablets 25mg/67,5 mg of Artesunate/Amodiaquine will be given to 124 trial patients.
 Drug: Artesunate/Amodiaquine

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

Other Name: Co-arsucam®
Active Comparator: Quinine + Clindamycin
Quinine tablet 125mg + Clindamycin syrup 75mg/5ml will be given to 60 children.
 Drug: Quinine + Clindamycin

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

Other Names:
  • Quinimax® tablet 125mg
  • Dalacin® syrup 75mg/5ml

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   12 Months to 59 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Have been enrolled in the first phase
  2. Recurrent Plasmodium falciparum infection with clinical symptoms.
  3. Parents' or guardians' willingness and ability to comply with the study protocol for the duration of the study.
  4. 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

Exclusion Criteria:

Patients with at least one of the following criteria will be excluded:

  1. Participation in any other investigational drug study (antimalarial or others) during the previous 30 days.
  2. Known hypersensitivity and previous Serious Adverse Events related to the study drugsto the study drugs.
  3. 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.
  4. 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.
  5. Patients who are taking drug which may prolong the QT (imidazole and triazole, antifungal agent).
  6. Severe malnutrition (defined as weight for height <70% of the median NCHS/WHO reference).
  7. Ongoing prophylaxis with drugs having antimalarial activity such as cotrimoxazole for the prevention of Pneumocisti carini pneumonia in children born to HIV+ women.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01374581

Contacts
Contact: Jean-Pierre Van geertruyden, MD MPH PhD ++ 32 32652528 Jean-Pierre.VanGeertruyden@ua.ac.be

Locations
Congo
Centre de Santé Lisungi Recruiting
Kinshasa, Mont-Ngafula, Congo, Route Kimwenza n°23
Principal Investigator: Hypolite Muhindo Mavoko, MD MPH            
Uganda
Kazo Health centre IV Recruiting
Kiruhura, Uganda, P.O Box 5 Rushere
Principal Investigator: Carolyn Nabasumba, M.B.Ch.B            
Sponsors and Collaborators
Universiteit Antwerpen
European and Developing Countries Clinical Trials Partnership (EDCTP)
Fund for Scientific Research, Flanders, Belgium
Institute of Tropical Medicine, Belgium
University of Kinshasa
Centre Muraz
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Makerere University
Investigators
Principal Investigator: Hypolite M. Mavoko, MD MPH Kinshasa University, RDCongo
Principal Investigator: Carolyn Nabasumba, M.B.Ch.B Kazo health centre IV Uganda
Study Director: Jean-Pierre Van geertruyden, MD MPH PhD International Health Unit Antwerp university
  More Information

No publications provided

Responsible Party: Jean-Pierre Van geertruyden, Prof, Universiteit Antwerpen
ClinicalTrials.gov Identifier: NCT01374581     History of Changes
Other Study ID Numbers: UA-IHU-2010-01 version 1
Study First Received: June 9, 2011
Last Updated: January 15, 2013
Health Authority: Belgium: Fund for Scientific Research, Flanders
Congo, Democratic Republic of the: Ministry of Health
Uganda: Ministry of Health

Keywords provided by Universiteit Antwerpen:
retreatment
artemisinin-based combination
malaria
resistant

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases
Amodiaquine
Quinine
Artemether
Artemisinins
Artesunate
Lumefantrine
Artemether-lumefantrine combination
Clindamycin-2-phosphate
Artemisinine
Clindamycin
Antimalarials
Antiprotozoal Agents
 Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Muscle Relaxants, Central
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Analgesics, Non-Narcotic
Analgesics

ClinicalTrials.gov processed this record on June 13, 2013