Artemisinin-Based Antimalarial Combinations and Clinical Response in Cameroon
Raktažodžiai
Santrauka
apibūdinimas
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.
Datos
| Paskutinį kartą patikrinta: | 08/31/2018 |
| Pirmasis pateikimas: | 04/27/2013 |
| Numatytas registravimas pateiktas: | 04/29/2013 |
| Pirmas paskelbtas: | 05/02/2013 |
| Paskutinis atnaujinimas pateiktas: | 09/23/2018 |
| Paskutinis atnaujinimas paskelbtas: | 09/25/2018 |
| Faktinė studijų pradžios data: | 02/28/2010 |
| Numatoma pirminio užbaigimo data: | 03/31/2014 |
| Numatoma studijų užbaigimo data: | 03/31/2015 |
Būklė ar liga
Intervencija / gydymas
Drug: Artesunate-Amodiaquine
Drug: Dihydroartemisinine_Piperaquine
Drug: Artemeter-Lumefantrine
Fazė
Rankų grupės
| Ranka | Intervencija / gydymas |
|---|---|
| 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 for 48H | 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®). |
| 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. |
| 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 tablets containing Artemether-Lumefantrine at (20mg/120mg) for body weights of 5-10kg every 12H within 48H. | Drug: Artemeter-Lumefantrine 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. |
Tinkamumo kriterijai
| Amžius, tinkami studijuoti | 6 Months Į 6 Months |
| Tinkamos studijoms lytys | All |
| Priima sveikus savanorius | Taip |
| Kriterijai | 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. |
Rezultatas
Pirminės rezultatų priemonės
1. Clinical Efficacy [42 days]
Antrinės rezultatų priemonės
1. Safety by measure of changes in Physiologic, Blood, Liver and Kidney functions to define AE & SAEs [42 days]
