Ignite Creation Date:
2024-05-05 @ 5:32 PM
Last Modification Date:
2024-10-26 @ 9:32 AM
Study NCT ID:
NCT00471705
Status:
COMPLETED
Last Update Posted:
2019-01-16
First Post:
2007-05-07
Brief Title:
Efficacy and Safety of Miltefosine or Thermotherapy for Cutaneous Leishmaniasis in Colombia
Sponsor:
Universidad de Antioquia
Organization:
Universidad de Antioquia
Study Overview
Official Title:
Phase 3 Open-label Study of Efficacy and Safety of Miltefosine or Thermotherapy vs Glucantime for Cutaneous Leishmaniasis in Colombia
Status:
COMPLETED
Status Verified Date:
2009-06
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:
None
Brief Summary:
Cutaneous leishmaniasis CL is a worldwide disease endemic in 88 countries that has shown an increasing incidence the last two decades It is estimated that in 2005 about of 20000 new cases of CL were diagnosed in Colombia
So far pentavalent antimony compounds have been considered the treatment of choice with a percentage of cure of about 85 However the high efficacy of these drugs is counteracted by their adverse events and disadvantages Previous studies have shown that miltefosine could be a potential alternative of treatment for CL
The main objective of this study is to evaluate the efficacy and safety of miltefosine or thermotherapy for the treatment for CL In this study the efficacy of oral treatment of miltefosine 150 mgday for 28 days or a thermotherapy device used for one session at 50 celsius degrees during 30 seconds will be compared with the standard treatment of intramuscular injections of 20 mgKgday of pentavalent antimonials GlucantimeÒ for 20 days in CL parasitologically proven patients
This trial will be conducted according to the International approved GCP Good Clinical Practice guidelines
So far pentavalent antimony compounds have been considered the treatment of choice with a percentage of cure of about 85 However the high efficacy of these drugs is counteracted by their adverse events and disadvantages Previous studies have shown that miltefosine could be a potential alternative of treatment for CL
The main objective of this study is to evaluate the efficacy and safety of miltefosine or thermotherapy for the treatment for CL In this study the efficacy of oral treatment of miltefosine 150 mgday for 28 days or a thermotherapy device used for one session at 50 celsius degrees during 30 seconds will be compared with the standard treatment of intramuscular injections of 20 mgKgday of pentavalent antimonials GlucantimeÒ for 20 days in CL parasitologically proven patients
This trial will be conducted according to the International approved GCP Good Clinical Practice guidelines
Detailed Description:
Evaluation of Efficacy and Safety of Miltefosine for Cutaneous Leishmaniasis in Colombia Leishmaniasis is taking dramatic dimensions in Colombia due to its rapid expansion reemergence which has made Colombia became in the second South American country in levels of annual incidence the appearance of new infection sources the entrance of the vector to the homes the urbanization of the disease the higher population in risk of infection the absence of adequate medications safe non-expensive easily available with oral or topic route of administration and the higher resistance to the only available medication for its treatment It is estimated that in 2005 more than 20000 new cases were diagnosed 10265 of them among the Colombian military forces personnel but it is well known that in most of the rural areas the major proportion of cases are not diagnosed and the people cannot reach to an adequate treatment and they have to use empiric options
On the other hand the Program for Research and Control in tropical diseases PECET is working among Tropical Diseases ResearchWorld Health OrganizationTDRWHO in the evaluation of drugs and vaccines against Leishmaniasis besides PECET belongs to the TDRWHO Clinical Monitors groups TDRWHO Data Management and participates in the Initiative for Public Health Products Development Doctorate among five Asiatic universities The Ministry of Social Protection is aware of the need of new therapeutic alternatives for Leishmaniasis and has requested to PECET to conduct a controlled clinical trial to determinate the efficacy and safety of Miltefosine compared with Glucantime for the treatment of Cutaneous Leishmaniasis CL in Colombia even though previous no conclusive trials conducted in Guatemala and Colombia have demonstrated efficacy this could be an alternative of treatment for this country
Thermomed is a battery-operated medical device that delivers precisely controlled localized current field radio frequency heat to selectively destroy certain diseased tissue Radio frequency energy is directed through the handset to the applicator that is placed in direct contact with the lesion the applicator contains a thermocouple to continuously monitor and control temperature to within 50º Celsius The thermomed has been used for research on treatment for cutaneous leishmaniasis and recent clinical studies have shown not only clinical improvement but also that therapy elicits an immune response to the disease Through this trial we will try to perform a conclusive clinical evaluation about this drug
In summary with this project to conduct a clinical trial to determine the efficacy and safety of Miltefosine or thermotherapy compared with Glucantime for treatment of CL in Colombian patients
Population CL in is a remerging disease in Colombia affecting civilian and military population as well sharing the same epidemiologic characteristics
The selected population will be composed from National Army of Colombia soldiers from CL endemic areas Caquetá Meta Guaviare Putumayo Córdoba Antioquia and Chocó
Treatment
In this phase III randomized open trial subjects meeting inclusion criteria of the trial will be randomly allocated into two groups according to a randomization list One group will be treated with 150 mgday of oral miltefosine for 28 days a second group will be treated with thermotherapy device used for one session at 50 celsius degrees during 30 seconds and a third group will be treated with intramuscular injections of 20 mgkgday Glucantime for 20 days A written instruction sheet will be given to each included patient and the patient will be instructed to contact the research team on appearance of symptoms suggesting severe side effects intractable diarrhea andor vomiting symptoms of liver kidney or hematopoietic system dysfunction Until six weeks after the termination of the treatment any patient who received oral miltefosine or was treated with thermotherapy and has active lesion will be treated with intramuscular Glucantime injections 20mgkgday for 20 days
Study development Schedule of activities Screening -2 or day 0 Protocol explanation invitation to participate inform consent signature parasitological diagnosis Direct test laboratory tests Complete hemogram Ureic Nitrogen BUN creatinine amylase Glutamic-pyruvic transaminaseGTP or ALT glutamic-oxaloacetic transaminaseGOT or AST
Inclusion Visit 1 Randomization sampling of Cultures physical examination vital signs measure oral treatment initiation Miltefosine for 28 days or Glucantime intramuscular application initiation for the 20 subsequent days or thermotherapy Local heat patients clinical record CRF Case Report Format fulfilling lesions picture taking
Visit 2 Middle of treatment Laboratory tests Complete hemogram BUN creatinine amylase GOT GPT physical examination vital signs measure CRF Case Report Format fulfilling Lesions picture taking
Visit 3 End of treatment 10 days Laboratory tests Complete hemogram BUN creatinine amylase GTP GOT physical examination vital signs measure CRF Case Report Format fulfilling lesions picture taking Evaluation of treatment efficacy
Visit 4 Six weeks after treatment 15 days Physical examination Vital signs measure CRF Case Report Format fulfilling lesions picture taking evaluation of treatment efficacy
Visit 5 Three months after treatment 30 days Physical examination Vital signs measure CRF Case Report Format fulfilling lesions picture taking evaluation of treatment efficacy
Visit 6 Six months after treatment 40 days Physical examination Vital signs measure CRF Case Report Format fulfilling lesions picture taking evaluation of treatment efficacy
Procedures
Physical examination A complete physical examination will be realized and vital signs will be measured
Blood samples withdrawn
Blood samples will be withdrawn from the antecubital vein to perform the following analyses
Creatinine and Blood Urea Nitrogen
Alanine transaminase ALT
Aspartate transaminase AST
Pancreatic amylase
Complete hemogram
Technique for the sampling of cultures The sample for the culture may be obtained by suctioning the ulcer active edge in a phosphate-buffered saline solution PBS with antibiotics 1000 IU of crystalline Penicillin per cc before it is put in the culture medium
A tuberculin syringe 05 cc of PBS solution with antibiotics is used in the suction technique Previous asepsis of the ulcer with alcohol at 70 a needle is introduced into the dermis and through rotating movements a small amount of tissue is macerated by the needle bevel during about a minute after which it is suctioned into the syringe The sample is deposited in aseptic conditions into a NNN Novy-MacNeal-Nicole culture medium and incubated at 26C during 4 weeks The strains are identified by species using the monoclonal antibodies
Toxicity
The grade of toxicity will be evaluated according the following parameters
Systemic Fever Headache
Gastrointestinal Nausea vomiting oral discomfort
Cardiovascular cardiac rhythm hypertension hypotension
Musculoskeletal Arthralgia joint pain myalgia
During the treatment and the follow-up visits the patients will be asked about adverse events Each adverse event will be classified by the physician as serious or non-serious A serious adverse event should meet one or more of the following criteria
Death
Life-threatening ie immediate risk of death
In-patient hospitalization or prolongation of existing hospitalization
Persistent or significant disabilityincapacity The presence of a serious adverse event that puts the patients life at risk andor requires immediate medical or surgical procedure will call for the discontinuation of the treatment and the initiation of the pertinent medical management of the patients The study staff will notify the Adverse IECIRB of the University of Antioquia of any serious adverse event within 24 hours of having knowledge of it
A non-serious adverse event will be classified as follows
Mild The patients are aware of their symptoms andor signs but those are tolerable They do not require medical intervention or specific treatment
Moderate Patients present troubles that interfere with their daily activities They require medical intervention or specific treatment
Severe The patients are unable to work or to attend their daily activities They require medical intervention or specific treatment
The possible relationship between the adverse events and the tested medication will be classified by the investigator on the basis of hisher clinical judgment and the following definitions
Definitely related Event can be fully explained by the administration of the tested medication
Probably related Event is most likely to be explained by the administration of the tested medication rather than other medications or by the patients clinical state
Possibly related Event may be explained by the administration of the tested medication or other medications or by the patients clinical state
Not related Event is most likely to be explained by the patients clinical state or other medications rather than the tested one
Data analysis phase The healing rate will be calculated according to each group treatment and control by intention to treat and by protocol Subgroups will be established depending on the clinical response adverse events and according to Leishmania specie Besides the characteristics of the lesion size localization type of lesion demographic characteristics and how long the healing takes after the treatment is settled
In all cases significance test will be performed to compare both treatments
Endpoints Primary Clinical response Complete re-epithelization of all lesions with disappearance of induration with or without scar No parasitological evaluation will be done on clinically cured lesions determined until 45 days posttreatment
Clinical improvement Reduction of a 50 area of induration and ulcer compared with immediately previous evaluation
Secondary
Treatment failure No change or increase in the size of induration and ulcer Absence of clinical response Induration and ulcer area 50 compared with the immediately previous evaluation
Final reports At the end of the study the results will be evaluated and discussed and a final report presented to Colombian army and Ministry of Social Protection entities sponsoring the project The relevant results will be published in both national and international journals and presented in congresses and scientific meetings
Ethical aspects This study will be conduced according with the Declaration of Helsinki the Colombian legislation as per the resolution 00843093 from the Ministry of Health Canadian Council of Animal Care National Institute for drugs and foods vigilance and control - INVIMAColombia International Conference on Harmonisation-Good Clinical Practice ICH-GCP guidelines and TDRWHO guidelines for clinical research
Prior to the admission of the patients in the study the objectives and the methodology will be explained and informed consent obtained
The study was approved for the Sede de Investigación Universitaria SIU bioethics committee CBEIH-SIU and the Leishmaniasis Committee of the Colombian Military Forces
The right to confidentiality of the patients will be maintained in all the phases of the study
Competing of interests
The authors declare that they have no competing of interests
On the other hand the Program for Research and Control in tropical diseases PECET is working among Tropical Diseases ResearchWorld Health OrganizationTDRWHO in the evaluation of drugs and vaccines against Leishmaniasis besides PECET belongs to the TDRWHO Clinical Monitors groups TDRWHO Data Management and participates in the Initiative for Public Health Products Development Doctorate among five Asiatic universities The Ministry of Social Protection is aware of the need of new therapeutic alternatives for Leishmaniasis and has requested to PECET to conduct a controlled clinical trial to determinate the efficacy and safety of Miltefosine compared with Glucantime for the treatment of Cutaneous Leishmaniasis CL in Colombia even though previous no conclusive trials conducted in Guatemala and Colombia have demonstrated efficacy this could be an alternative of treatment for this country
Thermomed is a battery-operated medical device that delivers precisely controlled localized current field radio frequency heat to selectively destroy certain diseased tissue Radio frequency energy is directed through the handset to the applicator that is placed in direct contact with the lesion the applicator contains a thermocouple to continuously monitor and control temperature to within 50º Celsius The thermomed has been used for research on treatment for cutaneous leishmaniasis and recent clinical studies have shown not only clinical improvement but also that therapy elicits an immune response to the disease Through this trial we will try to perform a conclusive clinical evaluation about this drug
In summary with this project to conduct a clinical trial to determine the efficacy and safety of Miltefosine or thermotherapy compared with Glucantime for treatment of CL in Colombian patients
Population CL in is a remerging disease in Colombia affecting civilian and military population as well sharing the same epidemiologic characteristics
The selected population will be composed from National Army of Colombia soldiers from CL endemic areas Caquetá Meta Guaviare Putumayo Córdoba Antioquia and Chocó
Treatment
In this phase III randomized open trial subjects meeting inclusion criteria of the trial will be randomly allocated into two groups according to a randomization list One group will be treated with 150 mgday of oral miltefosine for 28 days a second group will be treated with thermotherapy device used for one session at 50 celsius degrees during 30 seconds and a third group will be treated with intramuscular injections of 20 mgkgday Glucantime for 20 days A written instruction sheet will be given to each included patient and the patient will be instructed to contact the research team on appearance of symptoms suggesting severe side effects intractable diarrhea andor vomiting symptoms of liver kidney or hematopoietic system dysfunction Until six weeks after the termination of the treatment any patient who received oral miltefosine or was treated with thermotherapy and has active lesion will be treated with intramuscular Glucantime injections 20mgkgday for 20 days
Study development Schedule of activities Screening -2 or day 0 Protocol explanation invitation to participate inform consent signature parasitological diagnosis Direct test laboratory tests Complete hemogram Ureic Nitrogen BUN creatinine amylase Glutamic-pyruvic transaminaseGTP or ALT glutamic-oxaloacetic transaminaseGOT or AST
Inclusion Visit 1 Randomization sampling of Cultures physical examination vital signs measure oral treatment initiation Miltefosine for 28 days or Glucantime intramuscular application initiation for the 20 subsequent days or thermotherapy Local heat patients clinical record CRF Case Report Format fulfilling lesions picture taking
Visit 2 Middle of treatment Laboratory tests Complete hemogram BUN creatinine amylase GOT GPT physical examination vital signs measure CRF Case Report Format fulfilling Lesions picture taking
Visit 3 End of treatment 10 days Laboratory tests Complete hemogram BUN creatinine amylase GTP GOT physical examination vital signs measure CRF Case Report Format fulfilling lesions picture taking Evaluation of treatment efficacy
Visit 4 Six weeks after treatment 15 days Physical examination Vital signs measure CRF Case Report Format fulfilling lesions picture taking evaluation of treatment efficacy
Visit 5 Three months after treatment 30 days Physical examination Vital signs measure CRF Case Report Format fulfilling lesions picture taking evaluation of treatment efficacy
Visit 6 Six months after treatment 40 days Physical examination Vital signs measure CRF Case Report Format fulfilling lesions picture taking evaluation of treatment efficacy
Procedures
Physical examination A complete physical examination will be realized and vital signs will be measured
Blood samples withdrawn
Blood samples will be withdrawn from the antecubital vein to perform the following analyses
Creatinine and Blood Urea Nitrogen
Alanine transaminase ALT
Aspartate transaminase AST
Pancreatic amylase
Complete hemogram
Technique for the sampling of cultures The sample for the culture may be obtained by suctioning the ulcer active edge in a phosphate-buffered saline solution PBS with antibiotics 1000 IU of crystalline Penicillin per cc before it is put in the culture medium
A tuberculin syringe 05 cc of PBS solution with antibiotics is used in the suction technique Previous asepsis of the ulcer with alcohol at 70 a needle is introduced into the dermis and through rotating movements a small amount of tissue is macerated by the needle bevel during about a minute after which it is suctioned into the syringe The sample is deposited in aseptic conditions into a NNN Novy-MacNeal-Nicole culture medium and incubated at 26C during 4 weeks The strains are identified by species using the monoclonal antibodies
Toxicity
The grade of toxicity will be evaluated according the following parameters
Systemic Fever Headache
Gastrointestinal Nausea vomiting oral discomfort
Cardiovascular cardiac rhythm hypertension hypotension
Musculoskeletal Arthralgia joint pain myalgia
During the treatment and the follow-up visits the patients will be asked about adverse events Each adverse event will be classified by the physician as serious or non-serious A serious adverse event should meet one or more of the following criteria
Death
Life-threatening ie immediate risk of death
In-patient hospitalization or prolongation of existing hospitalization
Persistent or significant disabilityincapacity The presence of a serious adverse event that puts the patients life at risk andor requires immediate medical or surgical procedure will call for the discontinuation of the treatment and the initiation of the pertinent medical management of the patients The study staff will notify the Adverse IECIRB of the University of Antioquia of any serious adverse event within 24 hours of having knowledge of it
A non-serious adverse event will be classified as follows
Mild The patients are aware of their symptoms andor signs but those are tolerable They do not require medical intervention or specific treatment
Moderate Patients present troubles that interfere with their daily activities They require medical intervention or specific treatment
Severe The patients are unable to work or to attend their daily activities They require medical intervention or specific treatment
The possible relationship between the adverse events and the tested medication will be classified by the investigator on the basis of hisher clinical judgment and the following definitions
Definitely related Event can be fully explained by the administration of the tested medication
Probably related Event is most likely to be explained by the administration of the tested medication rather than other medications or by the patients clinical state
Possibly related Event may be explained by the administration of the tested medication or other medications or by the patients clinical state
Not related Event is most likely to be explained by the patients clinical state or other medications rather than the tested one
Data analysis phase The healing rate will be calculated according to each group treatment and control by intention to treat and by protocol Subgroups will be established depending on the clinical response adverse events and according to Leishmania specie Besides the characteristics of the lesion size localization type of lesion demographic characteristics and how long the healing takes after the treatment is settled
In all cases significance test will be performed to compare both treatments
Endpoints Primary Clinical response Complete re-epithelization of all lesions with disappearance of induration with or without scar No parasitological evaluation will be done on clinically cured lesions determined until 45 days posttreatment
Clinical improvement Reduction of a 50 area of induration and ulcer compared with immediately previous evaluation
Secondary
Treatment failure No change or increase in the size of induration and ulcer Absence of clinical response Induration and ulcer area 50 compared with the immediately previous evaluation
Final reports At the end of the study the results will be evaluated and discussed and a final report presented to Colombian army and Ministry of Social Protection entities sponsoring the project The relevant results will be published in both national and international journals and presented in congresses and scientific meetings
Ethical aspects This study will be conduced according with the Declaration of Helsinki the Colombian legislation as per the resolution 00843093 from the Ministry of Health Canadian Council of Animal Care National Institute for drugs and foods vigilance and control - INVIMAColombia International Conference on Harmonisation-Good Clinical Practice ICH-GCP guidelines and TDRWHO guidelines for clinical research
Prior to the admission of the patients in the study the objectives and the methodology will be explained and informed consent obtained
The study was approved for the Sede de Investigación Universitaria SIU bioethics committee CBEIH-SIU and the Leishmaniasis Committee of the Colombian Military Forces
The right to confidentiality of the patients will be maintained in all the phases of the study
Competing of interests
The authors declare that they have no competing of interests
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