Ignite Creation Date:
2024-05-06 @ 8:23 PM
Last Modification Date:
2024-10-26 @ 3:27 PM
Study NCT ID:
NCT06367361
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-12
First Post:
2024-03-22
Brief Title:
One and Two Doses of Oxfendazole Versus a Schedule of Two Doses of Triclabendazole in Chronic Fascioliasis
Sponsor:
Universidad Peruana Cayetano Heredia
Organization:
Universidad Peruana Cayetano Heredia
Study Overview
Official Title:
Non-inferiority Controlled Randomized Single-blind Study for Compare Regimens of One and Two Doses of Oxfendazole Versus a Schedule of Two Doses of Triclabendazole to Treat Chronic Fascioliasis
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
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:
Randomized clinical trial comparing the efficacy and safety of oxfendazole at 20 mgkg per dose in one and two dose regimens with a two-dose regimen of triclabendazole at 10 mgkg in an endemic region of the highlands of Peru Children and adults with fascioliasis in rural communities will be screened for inclusion and exclusion criteria and a total of 336 subjects 112 per study arm with chronic Fasciola infection will be enrolled and assigned randomly to the study arms in a 111 ratio The primary efficacy cure and egg reduction endpoints will be assessed on day 7 and 30 post treatment The secondary safety endpoint visits will be performed in days 0 3 7 and 30 post-treatment and Population Pharmacokinetics PK modeling studies will be performed in the first 24 hours after the first dose of oxfendazole
Detailed Description:
Quality Control and Quality Assurance Following a written Data Safety and Monitoring Board DSMB-accepted site quality management plan the participating site and the subcontractors will be responsible for conducting routine quality assurance and quality control activities to internally monitor study progress and protocol compliance The site principal investigator will provide direct access to all study-related sites source datadata collection forms and reports for the purpose of monitoring and auditing by the sponsor and inspection by local and regulatory authorities
The site principal investigator will ensure all study personnel are appropriately trained and applicable documentations are maintained on site The study principal investigator is the person primarily responsible for assuring compliance The study principal investigator will regularly review the study progress with team members and conduct periodic audits to ensure that informed consent has been obtained and documented The principal investigator will review the team operations and progress to ensure that study records are up to date complete and kept in a secure place accessible only to appropriate study personnel
Data Handling and Record Keeping The investigator is responsible to ensure the accuracy completeness legibility and timeliness of the data reported All source documents will be completed in a neat legible manner to ensure accurate interpretation of data
Data collection forms will be derived from the Case Report Forms CRF and provided to the study site to record and maintain the data for each subject enrolled in the study Data reported in the CRF derived from source documents will be consistent with the source documents or the discrepancies will be explained
The data collection is the responsibility of the clinical trial staff at the site under the supervision of the site principal investigator The investigator will maintain complete and accurate documentation for the trial All source documents and laboratory reports will be reviewed by the clinical team and data entry staff to ensure the accuracy and completeness Adverse Events AE will be graded assessed for severity and causality and reviewed by the site principal investigator or a designee
Data Capture Methods Clinical data including AE and Concomitant Medication ConMed and clinical laboratory data will be entered into a pre-designed Electronic Case Report Forms eCRF on REDCap The clinical data will be entered directly from the source documents The CRF can be considered as a source document
The access to the REDCap platform will be strictly limited to study staff The level of access and capabilities for creating new records and changing existing records will be assigned according to specific staff work and need For example laboratory staff will only have access to the CRF for reporting test results and not to the CRF where the intervention arm or assigned drug is documented Laboratory staff will not be able to make changes to any forms except the results form REDCaps log-in trail will allow the principal investigator to track access to the platform and the changes made to the record during the time logged-in The platform will be strictly password protected and limited to designated trial personnel Subjects will be assigned a unique identifier All subjects records or data sets transferred to the sponsor will contain the identifier only Subjects names or information that would identify the subject will not be transferred Quality control will be performed as outlined in Chapter 13 of the protocol The quality control procedures will be specified in the Manual of Procedures MoP and CRF guidance
Types of Data The data for this trial will include clinical demographic safety hematology and chemistry laboratory values neuroimaging MRI and results of stool egg counts
TimingReports Safety data will be reviewed by the DSMB per the DSMB charter for this trial The DSMB will review available safety data Interim statistical reports may be generated as deemed necessary and appropriate by the Division of Microbiology and Infectious Diseases DMID
Subjects found to have intestinal parasites in the final stool examination will be contacted and referred to a local health provider to receive standard of care therapy at no cost
Study Records Retention Study records and reports including but not limited to CRF source documents Informed Consent Forms ICF laboratory test results and study drug disposition records will be retained for at least 2 years after a marketing application is approved for the study product to treat fascioliasis If no application is filed or if the application is not approved for the study product records will be retained until 2 years after the investigation is discontinued and the FDA has been notified The documents will be retained for a longer period if required by local regulations ICF for future use will be maintained as long as the samplespecimen exists
No records will be destroyed without the written consent of the sponsor It is the responsibility of the sponsor to inform the site principal investigator when these documents no longer need to be retained
Sample Size Considerations The primary outcome for the study will be the parasitological cure rate of chronic fascioliasis assessed by the qualitative yesno results of the Kato Katz and a Rapid Sedimentation stool tests on Visit Day 30 A subject will be considered cured if the result is negative 0 eggsgr of stool at 30 days after treatment Thus a binomial response BR will be obtained where If stool microscopy 0 on Day 30 then BR 1 otherwise BR 0
The primary analysis will consist of the statistical comparisons between binomial proportions for the single dose Oxfendazole OXF arm versus the Triclabendazole TCBZ arm and the two dose OXF arm versus the TCBZ arm using the Chi square test statistic with an alpha 5 Assuming a cure rate of at least 90 for the single OXF dose arm and at least 90 in the TCBZ arm a sample size of n 112 per group will be able to exclude an effectiveness difference of 10 in favor of the TCBZ treatment with 80 power and a difference at five percent level of significance Similarly assuming the same effectiveness at least 90 for the double OXF dose arm and the TCBZ arm a sample size of n 112 per group will be able to exclude an effectiveness difference of 10 in favor of the TCBZ treatment with 85 power and a difference at five percent level of significance
Final Analysis Plan The efficacy analysis will be performed in a modified Intention-To-Treat approach All subjects who were randomized in the study and receive at least one dose of study medication will be considered evaluable and entered in the final analysis database Subjects in this population will be analyzed according to the group to which they were originally randomized The same criteria to define the population will be used for the safety analysis Subjects who do not complete outcome assessments will be considered treatment failures regardless of their randomization group and final status
Initially the distribution of baseline population characteristics collected in visit day 1 will be summarized according to the randomization arms using frequencies means SD medians interquartile range and ranges The characteristics of the groups will be compared using Chi square tests for categorical variables and the T-test ANOVA if indicated for the continuous variables The primary efficacy endpoint will be summarized as the percent of subjects with parasitological cure in each arm at visit day 30 The efficacy between groups will be compared using a Chi Square test with a p 005 to determine the significance off the differences The efficacy analyses will also be performed using generalized linear regression models to assess any possibility of effect modification and to adjust for any population study strataprovince and parasitological characteristic that may appeared to be unbalanced after randomization The egg reduction end point will be analyzed calculating the mean or median if indicated egg reduction for the treatment groups and comparing them using the T-Test or Mann-Whitney test if indicated Similarly the egg reduction tests results will be modeled using multiple generalized linear regression to account for imbalances between the groups Finally the absolute frequency of all AEs and specifically Serious Adverse Events SAE will be compared post-treatment versus baseline using Poisson models for count data to determine potential safety concerns The proportion of individuals with SAE will be also calculated and compared between arms A detailed Analysis Plan will be submitted to the Study DSMB for approval before any study activities are initiated
The site principal investigator will ensure all study personnel are appropriately trained and applicable documentations are maintained on site The study principal investigator is the person primarily responsible for assuring compliance The study principal investigator will regularly review the study progress with team members and conduct periodic audits to ensure that informed consent has been obtained and documented The principal investigator will review the team operations and progress to ensure that study records are up to date complete and kept in a secure place accessible only to appropriate study personnel
Data Handling and Record Keeping The investigator is responsible to ensure the accuracy completeness legibility and timeliness of the data reported All source documents will be completed in a neat legible manner to ensure accurate interpretation of data
Data collection forms will be derived from the Case Report Forms CRF and provided to the study site to record and maintain the data for each subject enrolled in the study Data reported in the CRF derived from source documents will be consistent with the source documents or the discrepancies will be explained
The data collection is the responsibility of the clinical trial staff at the site under the supervision of the site principal investigator The investigator will maintain complete and accurate documentation for the trial All source documents and laboratory reports will be reviewed by the clinical team and data entry staff to ensure the accuracy and completeness Adverse Events AE will be graded assessed for severity and causality and reviewed by the site principal investigator or a designee
Data Capture Methods Clinical data including AE and Concomitant Medication ConMed and clinical laboratory data will be entered into a pre-designed Electronic Case Report Forms eCRF on REDCap The clinical data will be entered directly from the source documents The CRF can be considered as a source document
The access to the REDCap platform will be strictly limited to study staff The level of access and capabilities for creating new records and changing existing records will be assigned according to specific staff work and need For example laboratory staff will only have access to the CRF for reporting test results and not to the CRF where the intervention arm or assigned drug is documented Laboratory staff will not be able to make changes to any forms except the results form REDCaps log-in trail will allow the principal investigator to track access to the platform and the changes made to the record during the time logged-in The platform will be strictly password protected and limited to designated trial personnel Subjects will be assigned a unique identifier All subjects records or data sets transferred to the sponsor will contain the identifier only Subjects names or information that would identify the subject will not be transferred Quality control will be performed as outlined in Chapter 13 of the protocol The quality control procedures will be specified in the Manual of Procedures MoP and CRF guidance
Types of Data The data for this trial will include clinical demographic safety hematology and chemistry laboratory values neuroimaging MRI and results of stool egg counts
TimingReports Safety data will be reviewed by the DSMB per the DSMB charter for this trial The DSMB will review available safety data Interim statistical reports may be generated as deemed necessary and appropriate by the Division of Microbiology and Infectious Diseases DMID
Subjects found to have intestinal parasites in the final stool examination will be contacted and referred to a local health provider to receive standard of care therapy at no cost
Study Records Retention Study records and reports including but not limited to CRF source documents Informed Consent Forms ICF laboratory test results and study drug disposition records will be retained for at least 2 years after a marketing application is approved for the study product to treat fascioliasis If no application is filed or if the application is not approved for the study product records will be retained until 2 years after the investigation is discontinued and the FDA has been notified The documents will be retained for a longer period if required by local regulations ICF for future use will be maintained as long as the samplespecimen exists
No records will be destroyed without the written consent of the sponsor It is the responsibility of the sponsor to inform the site principal investigator when these documents no longer need to be retained
Sample Size Considerations The primary outcome for the study will be the parasitological cure rate of chronic fascioliasis assessed by the qualitative yesno results of the Kato Katz and a Rapid Sedimentation stool tests on Visit Day 30 A subject will be considered cured if the result is negative 0 eggsgr of stool at 30 days after treatment Thus a binomial response BR will be obtained where If stool microscopy 0 on Day 30 then BR 1 otherwise BR 0
The primary analysis will consist of the statistical comparisons between binomial proportions for the single dose Oxfendazole OXF arm versus the Triclabendazole TCBZ arm and the two dose OXF arm versus the TCBZ arm using the Chi square test statistic with an alpha 5 Assuming a cure rate of at least 90 for the single OXF dose arm and at least 90 in the TCBZ arm a sample size of n 112 per group will be able to exclude an effectiveness difference of 10 in favor of the TCBZ treatment with 80 power and a difference at five percent level of significance Similarly assuming the same effectiveness at least 90 for the double OXF dose arm and the TCBZ arm a sample size of n 112 per group will be able to exclude an effectiveness difference of 10 in favor of the TCBZ treatment with 85 power and a difference at five percent level of significance
Final Analysis Plan The efficacy analysis will be performed in a modified Intention-To-Treat approach All subjects who were randomized in the study and receive at least one dose of study medication will be considered evaluable and entered in the final analysis database Subjects in this population will be analyzed according to the group to which they were originally randomized The same criteria to define the population will be used for the safety analysis Subjects who do not complete outcome assessments will be considered treatment failures regardless of their randomization group and final status
Initially the distribution of baseline population characteristics collected in visit day 1 will be summarized according to the randomization arms using frequencies means SD medians interquartile range and ranges The characteristics of the groups will be compared using Chi square tests for categorical variables and the T-test ANOVA if indicated for the continuous variables The primary efficacy endpoint will be summarized as the percent of subjects with parasitological cure in each arm at visit day 30 The efficacy between groups will be compared using a Chi Square test with a p 005 to determine the significance off the differences The efficacy analyses will also be performed using generalized linear regression models to assess any possibility of effect modification and to adjust for any population study strataprovince and parasitological characteristic that may appeared to be unbalanced after randomization The egg reduction end point will be analyzed calculating the mean or median if indicated egg reduction for the treatment groups and comparing them using the T-Test or Mann-Whitney test if indicated Similarly the egg reduction tests results will be modeled using multiple generalized linear regression to account for imbalances between the groups Finally the absolute frequency of all AEs and specifically Serious Adverse Events SAE will be compared post-treatment versus baseline using Poisson models for count data to determine potential safety concerns The proportion of individuals with SAE will be also calculated and compared between arms A detailed Analysis Plan will be submitted to the Study DSMB for approval before any study activities are initiated
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| U01AI155323 | NIH | None | httpsreporternihgovquickSearchU01AI155323 |