Ignite Creation Date:
2024-10-26 @ 3:41 PM
Last Modification Date:
2024-10-26 @ 3:41 PM
Study NCT ID:
NCT06622603
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-09-29
Brief Title:
The Effects of Febuxostat Dose Tapering in Gout Patients Optimally Controlled for 5 Years or More
Sponsor:
None
Organization:
None
Study Overview
Official Title:
A Prospective Multicenter Randomized Investigator Initiative Clinical Trial Study on the Effects of Febuxostat Dose Tapering in Gout Patients Optimally Controlled for 5 Years or More
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
TARGET
Brief Summary:
The goal of this clinical trial is to compare the changes in serum urate levels and symptom recurrence after reducing or suspending urate-lowering agents in well-controlled gout patients the after dishes are clean state in the Dirty Dish hypothesis
Researchers will compare three randomized groups the reducing group takes febuxostat 20 mg once daily for 12 months the discontinuing group takes a placebo once daily for 6 months followed by febuxostat 20 mg once daily for the next 6 months and the maintaining group continues their pre-study urate-lowering agents for 12 months serving as an observational reference group
During the 12-month study period participants will visit every 3 months for laboratory evaluations including serum urate levels and for checking symptomatic status using questionnaires and diaries Additionally musculoskeletal ultrasonography and serum sample collection will be performed at baseline to study predictors for maintaining serum urate levels 70 mgdL after reducing or suspending urate-lowering therapy
Researchers will compare three randomized groups the reducing group takes febuxostat 20 mg once daily for 12 months the discontinuing group takes a placebo once daily for 6 months followed by febuxostat 20 mg once daily for the next 6 months and the maintaining group continues their pre-study urate-lowering agents for 12 months serving as an observational reference group
During the 12-month study period participants will visit every 3 months for laboratory evaluations including serum urate levels and for checking symptomatic status using questionnaires and diaries Additionally musculoskeletal ultrasonography and serum sample collection will be performed at baseline to study predictors for maintaining serum urate levels 70 mgdL after reducing or suspending urate-lowering therapy
Detailed Description:
1 Background
1 Hyperuricemia is a condition that underlies the development of gout Gout incidence has been reported as 11 with urate levels 6 mgdL and 3 with urate levels between 6-7 mgdL in longitudinal studies However few studies have examined the incidence after suspending urate-lowering therapy following long-term maintenance of serum urate 6 mgdL
2 A US study found that gout patients who maintained serum urate 60 mgdL for over 5 years and had resolved tophi did not experience flare-ups if levels remained 7 mgdL while recurrence occurred in those with levels 7 mgdL Based on these findings the study proposed a two-stage gout treatment strategy known as the dirty dish hypothesis
3 The approved minimum dose of febuxostat is 40 mgday Previous studies observed that febuxostat 20 mgday reduced serum urate levels to 70 mgdL although it did not meet the current treatment goal during the initial phase
4 Therefore a low dose of febuxostat at 20 mgday could be sufficient to meet the preventive treatment goal of 7 mgdL proposed by the dirty dish hypothesis
2 Sample size determination
1 Average serum urate levels and standard deviations were extracted from 2 previous clinical trials for febuxostat including 20 mgday dose and 3 observational studies on the effects of complete discontinuation of urate-lowering agents The proportion of patients with serum uric acid levels 70 mgdL was calculated using the normal distribution curve
2 Based on previous studies we assumed that the smallest proportion of subjects with serum urate 70 mgdL is 5 for the discontinuing group and 56 for the reducing group Fishers exact test 1-β 080 α 005 21 ratio indicates that 12 subjects are needed for the discontinuing group and 24 for the reducing group Adjusting for a 15 dropout rate the final numbers are 15 and 29 respectively
3 The urate-lowering therapy-maintaining group is expected to have a 100 rate of serum urate 70 mgdL as they are treated according to current guidelines Therefore in the case of the maintaining group 15 subjects - half the number in the discontinuing group - will be assigned to this group without statistical calculation
2 General principles of statistical analysis
1 Categorical variables will be presented as frequencies and percentages with 95 CIs if needed Chi-square tests and Fishers exact tests will be used for categorical outcomes For missing data or withdrawals the analysis will use available data replacing missing values with the previous measurement
2 Analysis population
1 SAS Safety Analysis Set Includes all participants who received at least one dose of the investigational drug Safety data analysis will be conducted using SPSS or R
2 FAS Full Analysis Set or Intention-to-Treat Set Includes participants who received at least one dose of the drug and have available primary outcome data serum urate levels before and after treatment
3 PPS Per-Protocol Set Consists of FAS participants with no major protocol violations such as significant inclusionexclusion criteria breaches prohibited medication use or adherence issues Efficacy analysis will be primarily conducted with the PPS with additional analysis in the FAS
3 Efficacy analysis The primary analysis population is the PPS with sensitivity analysis conducted in the FAS
4 Safety analysis The primary analysis population is the SAS Descriptive statistics will be presented and analyzed for all adverse events occurring after the administration of the investigational drug as well as for clinical laboratory results vital signs physical examinations electrocardiograms and liver function tests
1 Hyperuricemia is a condition that underlies the development of gout Gout incidence has been reported as 11 with urate levels 6 mgdL and 3 with urate levels between 6-7 mgdL in longitudinal studies However few studies have examined the incidence after suspending urate-lowering therapy following long-term maintenance of serum urate 6 mgdL
2 A US study found that gout patients who maintained serum urate 60 mgdL for over 5 years and had resolved tophi did not experience flare-ups if levels remained 7 mgdL while recurrence occurred in those with levels 7 mgdL Based on these findings the study proposed a two-stage gout treatment strategy known as the dirty dish hypothesis
3 The approved minimum dose of febuxostat is 40 mgday Previous studies observed that febuxostat 20 mgday reduced serum urate levels to 70 mgdL although it did not meet the current treatment goal during the initial phase
4 Therefore a low dose of febuxostat at 20 mgday could be sufficient to meet the preventive treatment goal of 7 mgdL proposed by the dirty dish hypothesis
2 Sample size determination
1 Average serum urate levels and standard deviations were extracted from 2 previous clinical trials for febuxostat including 20 mgday dose and 3 observational studies on the effects of complete discontinuation of urate-lowering agents The proportion of patients with serum uric acid levels 70 mgdL was calculated using the normal distribution curve
2 Based on previous studies we assumed that the smallest proportion of subjects with serum urate 70 mgdL is 5 for the discontinuing group and 56 for the reducing group Fishers exact test 1-β 080 α 005 21 ratio indicates that 12 subjects are needed for the discontinuing group and 24 for the reducing group Adjusting for a 15 dropout rate the final numbers are 15 and 29 respectively
3 The urate-lowering therapy-maintaining group is expected to have a 100 rate of serum urate 70 mgdL as they are treated according to current guidelines Therefore in the case of the maintaining group 15 subjects - half the number in the discontinuing group - will be assigned to this group without statistical calculation
2 General principles of statistical analysis
1 Categorical variables will be presented as frequencies and percentages with 95 CIs if needed Chi-square tests and Fishers exact tests will be used for categorical outcomes For missing data or withdrawals the analysis will use available data replacing missing values with the previous measurement
2 Analysis population
1 SAS Safety Analysis Set Includes all participants who received at least one dose of the investigational drug Safety data analysis will be conducted using SPSS or R
2 FAS Full Analysis Set or Intention-to-Treat Set Includes participants who received at least one dose of the drug and have available primary outcome data serum urate levels before and after treatment
3 PPS Per-Protocol Set Consists of FAS participants with no major protocol violations such as significant inclusionexclusion criteria breaches prohibited medication use or adherence issues Efficacy analysis will be primarily conducted with the PPS with additional analysis in the FAS
3 Efficacy analysis The primary analysis population is the PPS with sensitivity analysis conducted in the FAS
4 Safety analysis The primary analysis population is the SAS Descriptive statistics will be presented and analyzed for all adverse events occurring after the administration of the investigational drug as well as for clinical laboratory results vital signs physical examinations electrocardiograms and liver function tests
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