Artemisinin-Based Antimalarial Combinations and Clinical Response in Cameroon

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by University of Yaounde 1
Sponsor:
Collaborators:
World Health Organization
Gates Malaria Partnership
Information provided by (Responsible Party):
Wilfred F. Mbacham, ScD, University of Yaounde 1
ClinicalTrials.gov Identifier:
NCT01845701
First received: April 28, 2013
Last updated: April 30, 2013
Last verified: April 2013
  Purpose

To assess the efficacy of artesunate-amodiaquine, dihydroartemisinin-piperaquine, in comparison with artemether-lumefantrine during 42 days follow up period in 720 children with acute uncomplicated P. falciparum malaria, in two different endemic ecological areas - Savanna and equatorial forest regions of Cameroon.

We have set as specific objectives:

  • To assess the efficacy of artesunate-amodiaquine, dihydroartemisinin-piperaquine, in comparison with artemether-lumefantrine during 14 and 28 days follow up period in children with acute uncomplicated P. falciparum malaria in two different endemic areas.
  • To evaluate the safety of artesunate-amodiaquine, dihydroartemisinin-piperaquine, in comparison with artemether-lumefantrine during 42 days follow up period in children with acute uncomplicated P. falciparum malaria.
  • To determine parasite clearance time (PCT) and fever clearance time (FCT) following the administration of the three trial regimens.
  • To investigate the treatment response based on WHO criteria (WHO, 2003) in patients in all groups after trial.
  • To investigate the Single Nucleotide Polymorphisms (SNPs) and microsatellite markers of genes associated with drug resistance

Condition Intervention Phase
Malaria
Drug: Artesunate-Amodiaquine
Drug: Dihydroartemisinine-Piperaquine
Drug: Artemether-lumefantrine combination
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: Phase III Study to Study the Clinical Response to ACT Fixed Dose Combination in 42 Days in Uncomplicated Malaria in Cameroon

Resource links provided by NLM:


Further study details as provided by University of Yaounde 1:

Primary Outcome Measures:
  • Clinical Efficacy [ Time Frame: 42 days ] [ Designated as safety issue: No ]
    Patient's trial outcome will be classified according to the WHO guidelines (WHO 2003) with application as follows: Early Treatment Failure (ETF); Late Clinical Failure (LCF); Late Parasitological Failure (LPF); Adequate Clinical and Parasitological Response (ACPR) - Absence of parasitaemia on day 42 irrespective of temperature without previously meeting any of the criteria of early treatment failure or late clinical failure or late parasitological failure


Secondary Outcome Measures:
  • Safety [ Time Frame: 42 days ] [ Designated as safety issue: Yes ]

    Prevalence of adverse events (AEs) and serious adverse events (SAEs): proportion of patients who experience AEs or SAEs during the follow up period of 42 days.

    Changes in vital parameters (blood pressure, pulse rate): proportion of patients who have significant changes in vital signs comparing to baseline during the follow up period of 42 days.

    Prevalence of abnormal laboratory tests: proportion of patients who have abnormal values of laboratory tests during the follow up period of 42 days.



Estimated Enrollment: 720
Study Start Date: March 2010
Estimated Study Completion Date: October 2013
Estimated Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Artesunate-Amodiaquine
As a fixed-dose combination of artesunate-amodiaquine developed by Sanofi-Aventis (France). It has the advantage of being a 3-day regimen usable by all age groups and potentially low cost. tablets are administered per every day at dose of 25mg/67.5mg for those between 4,5kg and 9kg.
Drug: Artesunate-Amodiaquine

Pharmacology: Amodiaquine is effective against the erythrocytic stages of all four species of P. falciparum. Amodiaquine accumulates in the parasite's lysosomes and prevents breakdown of haemoglobin on which the parasite depends for its survival.

Artesunate is a water-soluble hemisuccinate derivative of artemisinin. Artesunate and its active metabolite dihydroartemisinin are potent blood schizonticides, active against the ring stage of the parasite.

The fixed-dose combination dihydroartemisinin-piperaquine has a cost advantage over other ACTs that brings it within reach of many, making it a potential best candidate for deployment in Africa and other poor countries. The drug is currently produced in China (Duo-cotecxin®).

Other Name: CoArsucam
Experimental: Dihydroartemisinine_Piperaquine
As a fixed-dose combination of dihydroartemisinin-piperaquine which is produced by Fouley (China). It is a potentially low cost 2-day regimen that has been used in children between 5-10kg as half a tablet of 40mg/320mg every day for 48H
Drug: Dihydroartemisinine-Piperaquine
It is a bisquinoline antimalarial drug (1,3-bis[1-(7-chloro-4 quinolyl)-4- piperazinyl]-propane) that was first synthesised in the 1960s, and used extensively in China and Indochina as prophylaxis and treatment during the next 20 years. A number of Chinese research groups documented that it was at least as effective as, and better tolerated than, chloroquine against falciparum and vivax malaria. With the development of piperaquine-resistant strains of P. falciparum and the emergence of the artemisinin derivatives, its use declined during the 1980s. However, during the next decade, piperaquine was rediscovered by Chinese scientists as one of a number of compounds suitable for combination with an artemisinin derivative.
Other Name: Duo-Cotecxin
Active Comparator: Artemeter-Lumefantrine
This is the active comparator as a fixed-dose combination of artemether and lumefantrine which is produced by Novartis (Switzerland). The drug will be used as the comparator because it is the only fixed-dose combination with artemether currently available. Administered in children as a a tablet containing Artemether-Lumefantrine at (20mg/120mg) for body weights of 5-10kg.
Drug: Artemether-lumefantrine combination
CoArtem® is an oral, fixed combination of artemether- a derivative of artemisinin and lumefantrine- a novel molecule developed by the Academy of Military Medical Sciences (AMMS) in Beijing. It is the only co-formulated ACT approved by WHO and is currently available through WHO at a negotiated public sector price. Both compounds are effective as single agents. However, recrudescence is common with artemether and lumefantrine has a slow onset of action. A fixed combination tablet (20 mg artemether/120 mg lumefantrine) has therefore been developed. Fixed combination therapy improves compliance and has the advantage of carrying a lower risk of selecting drug resistant strains. No resistance to either component has been observed to date.
Other Name: CoArtem

Detailed Description:

Methodology Children of either gender, between 6 months (> 5kg) and 10 years of age, with acute uncomplicated P. falciparum infection, who fulfil all of the inclusion and have none of exclusion criteria will be enrolled in the study. They will be randomised to receive the three trial arms, i.e, Study Arm-A: artesunate-amodiaquine, Study Arm-B: dihydroartemisinin-piperaquine and Study Arm-C: artemether-lumefantrine at the ratio of 2:2:1 and will be hospitalised over a 3-day period to facilitate the supervised administration of the study drugs and full clinical and laboratory assessment and observation of early adverse effects. On discharge, participants will be required to report to the study clinic on days 7, 14, 21,28, 35 and 42 or at any other time when clinical sign(s)/symptom(s) of malaria is suspected. The number of participants is about 720 children

Inclusion Criteria

  • Children of either gender, aged between 6 months (> 5kg) and 10 years.
  • Suffering from acute uncomplicated P. falciparum malaria confirmed by microscopy using Giemsa-stained thick film with an asexual parasite density of 1,000 to 100,000 parasites/μl.
  • Presenting with fever (axillary temperature ≥ 37.5oC) or having a history of fever in the preceding 24 hours.
  • Able to ingest tablets orally (either suspended in water or uncrushed with food).
  • Willing to participate in the study with written assent from parent/guardian. Parental authorization will be obtained for children less than 8 years old and documented assent of parents/guardians for children 8-10 years.
  • Willing and able to attend the clinic on stipulated regular follow-up visits.

Exclusion Criteria

• Any of the following "danger signs of severe malaria": Not able to drink or breast feed Persistent vomiting (>2 episodes within previous 24 hours) Convulsions (>1 episode within previous 24 hours) Lethargic/unconscious

  • Signs/symptoms indicating severe/complicated malaria according to WHO criteria (WHO definition).
  • Concomitant illnesses, underlying chronic hepatic or renal disease, abnormal cardiac rhythm, hypoglycaemia, jaundice, respiratory distress,
  • Serious gastrointestinal disease, severe malnutrition (W/H < 70%) or severe anaemia (haemoglobin < 5 g/dl).
  • Known hypersensitivity to the study drugs.
  Eligibility

Ages Eligible for Study:   6 Months to 120 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Children of either gender, aged between 6 months (> 5kg) and 10 years.
  • Suffering from acute uncomplicated P. falciparum malaria confirmed by microscopy using Giemsa-stained thick film with an asexual parasite density of 1,000 to 100,000 parasites/μl.
  • Presenting with fever (axillary temperature ≥ 37.5oC) or having a history of fever in the preceding 24 hours.
  • Able to ingest tablets orally (either suspended in water or uncrushed with food).
  • Willing to participate in the study with written assent from parent/guardian. Parental authorization will be obtained for children less than 8 years old and documented assent of parents/guardians for children 8-10 years.
  • Willing and able to attend the clinic on stipulated regular follow-up visits.

Exclusion Criteria:

•Any of the following "danger signs of severe malaria": Not able to drink or breast feed Persistent vomiting (>2 episodes within previous 24 hours) Convulsions (>1 episode within previous 24 hours) Lethargic/unconscious

  • Signs/symptoms indicating severe/complicated malaria according to WHO criteria (WHO definition).
  • Concomitant illnesses, underlying chronic hepatic or renal disease, abnormal cardiac rhythm, hypoglycaemia, jaundice, respiratory distress,
  • Serious gastrointestinal disease, severe malnutrition (W/H < 70%) or severe anaemia (haemoglobin < 5 g/dl).
  • Known hypersensitivity to the study drugs.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01845701

Contacts
Contact: Wilfred F Mbacham, ScD +237-77579180 wfmbacham@yahoo.com
Contact: Akindeh M Nji, MSc +237-75354405 akindeh@yahoo.com

Locations
Cameroon
L'Hopital de District Ngong, Garoua, Recruiting
Garoua, North, Cameroon
Contact: Clifford Ebong, MD    237-77655876    clifebong@yahoo.com   
Contact: Olivier Ngongang, PharmD    +237-33106141    ericoliviern@yahoo.fr   
Sub-Investigator: Olivier Ngongang, PharmD         
Baptist Hospital Active, not recruiting
Mutengene, South West, Cameroon
Sponsors and Collaborators
University of Yaounde 1
World Health Organization
Gates Malaria Partnership
Investigators
Principal Investigator: Wilfred F Mbacham, ScD University of Yaounde 1
  More Information

No publications provided

Responsible Party: Wilfred F. Mbacham, ScD, PI, University of Yaounde 1
ClinicalTrials.gov Identifier: NCT01845701     History of Changes
Other Study ID Numbers: A60041
Study First Received: April 28, 2013
Last Updated: April 30, 2013
Health Authority: Cameroon: Ministry of Public Health

Keywords provided by University of Yaounde 1:
malaria, cure rate, efficacy, safety

Additional relevant MeSH terms:
Protozoan Infections
Malaria
Parasitic Diseases
Amodiaquine
Antimalarials
Artemether
Artemisinins
Artesunate
Dihydroquinghaosu
Piperaquine
Lumefantrine
Artemether-lumefantrine combination
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Coccidiostats
Schistosomicides
Antiplatyhelmintic Agents
Anthelmintics
Amebicides

ClinicalTrials.gov processed this record on July 20, 2014