Ignite Creation Date:
2024-05-06 @ 4:07 PM
Last Modification Date:
2024-10-26 @ 2:04 PM
Study NCT ID:
NCT04877626
Status:
COMPLETED
Last Update Posted:
2021-05-07
First Post:
2010-06-24
Brief Title:
Assessment of the Therapeutic Efficacy and Tolerability of the ArtesunateAmodiaquina Combination and ArtemetherLumefantrine Combination Treatment of Uncomplicated P Falciparum Malaria in the Department of Chocó Colombia
Sponsor:
Universidad Nacional de Colombia
Organization:
Universidad Nacional de Colombia
Study Overview
Official Title:
Assessment of the Therapeutic Efficacy and Tolerability of the ArtesunateAmodiaquina Combination and ArtemetherLumefantrine Combination the Standard Treatment Recommended by the Ministry of the Social Protection in Colombia for the Treatment of Uncomplicated P Falciparum Malaria in the Department of Chocó Colombia
Status:
COMPLETED
Status Verified Date:
2021-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
UNAL MALARIA
Brief Summary:
Background Malaria by P falciparum is a public health problem in more than 100 municipalities of Colombia The country is using the artemetherlumefantrine AML fixed combination for uncomplicated P falciparum malaria but it is ideal to have different types of formulations with similar efficacy that may be used in diverse circumstances One alternative of treatment is using preparations containing artesunate and amodiaquine ASAQ in fixed combination which can be given in a simpler dosing regimen In order to assess the efficacy of that combination in an area with suspected risk of resistance to amodiaquine an open controlled clinical trial was carried out in Colombia Methods The study was done in Choco a high endemic area for malaria by P falciparum from August 2008 and September 2009 Patients diagnosed with uncomplicated malaria n210 malaria were randomized in two arms one receiving ASAQ and the other AML The main clinical results was parasitological cure ie a negative blood smears that was assessed for both groups at days 1 2 3 7 14 21 and 28 after the onset of treatment Results There were no losses at follow up The mean age of the enrolled study subjects was of 375 years without differences between study arms Both therapies were very well tolerated in general The efficacy for ASAQ was 100 and 99 for AML p01 In average patients in the ASAQ arm became negative for P falciparum parasites and gametocytes earlier than those at the AML arm Blood smears became negative after one day of treatment with ASAQ and after two days of treatment with AML Gametocytes disappeared after 2 days of treatment in the ASAQ arm compared to 4 days in the AML arm Conclusions In this study the efficacy of the ASAQ combination was similar to that of the AML This finding do not support the hypothesis that there is a level of resistance to amodiaquine that prevents its use combined with artemisinin derived
Detailed Description:
Design An open-labeled randomized and controlled clinical trial with follow-up in days 1 2 3 4 7 14 21 and 28 was carried out in adult patients with uncomplicated P falciparum malaria This type of study has been validated by PAHO and has been used by the Amazon Network for the Surveillance of Antimalarial Drug RAVREDA to evaluate the efficacy of antimalarial treatment in the Americas region This study is a simplified version with monthly follow-up by a Data Safety Monitoring Board DSMB of the status of therapeutic failures to assure that the study progress does not result unethical
Study area The study area was in Department of Chocó which is located west in the Pacific region of the country has an approximate extension of 47000 Km2 equivalent to 4 of the countrys total extension Chocó has 31 Municipalities for a total of 454030 inhabitants according to the 2005 Survey From this population 90 is black 6 mulatto or white and the remaining 4 natives The great part of the population has its settling in the river and sea zones which constitutes an important aspect to consider in communications culture and socioeconomic development of the region The temperature ranges between 26º and 30ºC Patients were recruited from two municipalities Quibdo and Tado
Inclusion Criteria Age 18 years fever axillary temperature 375º C or history of fever during the prior 48 hours in absence of another obvious cause such as pneumonia otitis media a non-mixed P falciparum infection with 250 and 100000 asexual parasitesµl to be determined by a thick film or thick film and blood smear microscopic test
Exclusion Criteria Not being able to drink vomiting more than twice within the prior 24 hours recent history of seizures 1 or more in the previous 24 hours alteration of the consciousness level not being able to seat or stand up signs of serious malaria World Health Organization criteria other chronic or severe diseases ie cardiac renal and hepatic diseases HIVAIDS severe malnutrition history of hypersensibility to any of the study drugs or drugs used as alternative treatment ie mefloquine artesunate quinine or tetracyclineclindamycin and suspicion of pregnancy or pregnancy based on a urine pregnancy test
Study arms and treatments Two study arms were considered Group 1 received the combination AQAS COARSUCAM which was administered orally at an initial dose of 2 tablets 200 mg AQ540 mg AS followed by 2 additional doses of 2 tablets at 24 and 48 hours 6 tablets in 48 hours
Group 2 received the combination Artemeterlumefantrina COARTEM administered orally at an initial dose of 4 tablets 80 mg artemeter480 mg lumefantrina followed by 5 additional doses of 4 tablets at 8 24 36 48 and 60 hours 24 tablets in 60 hours
Sample size The sample size was estimated based on the expected proportion of failures for each one of the treatments in this population Assuming a similar efficacy for both treatments 7 and considering a proportion of failures to treatment of 5 range 1-11 in a population of infinite size a 5 significance level and a maximum tolerable error of 4 a total of 100 study subjects are required to be included in each group If 5 of the study subjects are lost in a 28 days study a total of 105 will be needed in each group All included subjects signed the Informed Consent
Randomization The assignment of treatments was made through a negative coordinated type sampling scheme 7 which consists in generating a list of randomized numbers from a normal distribution 01 and order the study subjects regarding this new list These ordered study subjects were systematically chosen in this case applying a ½ sampling fraction ie 1 of every two for each treatment arm since there were two arms with an initial number randomly generated through a Bernoulli distribution This process ensures a balanced allocation to the study arms
Main outcomes failure to take the drug on any of the first three days parasitemia on day 2 greater than that on day 0 presence of parasitemia on day 7 diagnosis of severe malaria at any point after day 0 recurrent parasitemia after day 7 up to day 28 8-11
Analysis Data were double-entered and validated using Epi info 2000 and the analysis was done using Stata 100 Per protocol analysis included patients who were properly randomised had received the study drugs according to the protocol and for whom data were available on the primary end point All statistical tests were two-sided and an α-level 005 was considered a statistically significant result For comparisons of continuous variables between groups the t-test was used and for comparisons between more than two groups one-way analysis of variance was used after assuring normality and homogeneity of variances assumptions were satisfied For comparison of categorical variables the chi-square test was used with the exact extension invoked when there were small numbers in the cells The end points were any of the following failure to take the drug on any of the first three days parasitaemia on day 2 greater than that on day 0 presence of parasitaemia on day 7 diagnosis of severe malaria at any point after day 0 recurrent parasitaemia after day 7 up to day 28
Study area The study area was in Department of Chocó which is located west in the Pacific region of the country has an approximate extension of 47000 Km2 equivalent to 4 of the countrys total extension Chocó has 31 Municipalities for a total of 454030 inhabitants according to the 2005 Survey From this population 90 is black 6 mulatto or white and the remaining 4 natives The great part of the population has its settling in the river and sea zones which constitutes an important aspect to consider in communications culture and socioeconomic development of the region The temperature ranges between 26º and 30ºC Patients were recruited from two municipalities Quibdo and Tado
Inclusion Criteria Age 18 years fever axillary temperature 375º C or history of fever during the prior 48 hours in absence of another obvious cause such as pneumonia otitis media a non-mixed P falciparum infection with 250 and 100000 asexual parasitesµl to be determined by a thick film or thick film and blood smear microscopic test
Exclusion Criteria Not being able to drink vomiting more than twice within the prior 24 hours recent history of seizures 1 or more in the previous 24 hours alteration of the consciousness level not being able to seat or stand up signs of serious malaria World Health Organization criteria other chronic or severe diseases ie cardiac renal and hepatic diseases HIVAIDS severe malnutrition history of hypersensibility to any of the study drugs or drugs used as alternative treatment ie mefloquine artesunate quinine or tetracyclineclindamycin and suspicion of pregnancy or pregnancy based on a urine pregnancy test
Study arms and treatments Two study arms were considered Group 1 received the combination AQAS COARSUCAM which was administered orally at an initial dose of 2 tablets 200 mg AQ540 mg AS followed by 2 additional doses of 2 tablets at 24 and 48 hours 6 tablets in 48 hours
Group 2 received the combination Artemeterlumefantrina COARTEM administered orally at an initial dose of 4 tablets 80 mg artemeter480 mg lumefantrina followed by 5 additional doses of 4 tablets at 8 24 36 48 and 60 hours 24 tablets in 60 hours
Sample size The sample size was estimated based on the expected proportion of failures for each one of the treatments in this population Assuming a similar efficacy for both treatments 7 and considering a proportion of failures to treatment of 5 range 1-11 in a population of infinite size a 5 significance level and a maximum tolerable error of 4 a total of 100 study subjects are required to be included in each group If 5 of the study subjects are lost in a 28 days study a total of 105 will be needed in each group All included subjects signed the Informed Consent
Randomization The assignment of treatments was made through a negative coordinated type sampling scheme 7 which consists in generating a list of randomized numbers from a normal distribution 01 and order the study subjects regarding this new list These ordered study subjects were systematically chosen in this case applying a ½ sampling fraction ie 1 of every two for each treatment arm since there were two arms with an initial number randomly generated through a Bernoulli distribution This process ensures a balanced allocation to the study arms
Main outcomes failure to take the drug on any of the first three days parasitemia on day 2 greater than that on day 0 presence of parasitemia on day 7 diagnosis of severe malaria at any point after day 0 recurrent parasitemia after day 7 up to day 28 8-11
Analysis Data were double-entered and validated using Epi info 2000 and the analysis was done using Stata 100 Per protocol analysis included patients who were properly randomised had received the study drugs according to the protocol and for whom data were available on the primary end point All statistical tests were two-sided and an α-level 005 was considered a statistically significant result For comparisons of continuous variables between groups the t-test was used and for comparisons between more than two groups one-way analysis of variance was used after assuring normality and homogeneity of variances assumptions were satisfied For comparison of categorical variables the chi-square test was used with the exact extension invoked when there were small numbers in the cells The end points were any of the following failure to take the drug on any of the first three days parasitaemia on day 2 greater than that on day 0 presence of parasitaemia on day 7 diagnosis of severe malaria at any point after day 0 recurrent parasitaemia after day 7 up to day 28
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None