Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04877626 |
| Other study ID # |
Treatment malaria in Colombia |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
September 2008 |
| Est. completion date |
December 2009 |
Study information
| Verified date |
May 2021 |
| Source |
Universidad Nacional de Colombia |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Background: Malaria by P falciparum is a public health problem in more than 100
municipalities of Colombia. The country is using the artemether+lumefantrine (AM+L) 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 (AS+AQ) 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 (n=210) malaria were randomized in two arms,
one receiving AS+AQ and the other AM+L. The main clinical results was parasitological cure,
i.e. 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 37.5 years without differences between study arms. Both
therapies were very well tolerated in general. The efficacy for AS+AQ was 100%, and 99% for
AM+L (p>0.1). In average, patients in the AS+AQ arm became negative for P falciparum
parasites and gametocytes earlier than those at the AM+L arm. Blood smears became negative
after one day of treatment with AS+AQ and after two days of treatment with AM+L. Gametocytes
disappeared after 2 days of treatment in the AS+AQ arm compared to 4 days in the AM+L arm.
Conclusions: In this study, the efficacy of the AS+AQ combination was similar to that of the
AM+L. This finding do not support the hypothesis that there is a level of resistance to
amodiaquine that prevents its use combined with artemisinin derived.
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 47,000 Km2, equivalent to 4% of the
country's total extension. Chocó has 31 Municipalities for a total of 454,030 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 >37.5º 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 100,000 asexual parasites/µl 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 (i.e., cardiac, renal and
hepatic diseases, HIV/AIDS, severe malnutrition), history of hypersensibility to any of the
study drugs or drugs used as alternative treatment (i.e. mefloquine, artesunate, quinine or
tetracycline/clindamycin), 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
AQ+AS (COARSUCAM®) which was administered orally at an initial dose of 2 tablets (200 mg
AQ/540 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 Artemeter+lumefantrina (COARTEM®) administered orally at an
initial dose of 4 tablets (80 mg artemeter/480 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 [0,1] and order the study subjects regarding this new list. These ordered study
subjects were systematically chosen (in this case applying a ½ sampling fraction, i.e., 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™ 10.0. 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 <0.05 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.
