Ignite Creation Date:
2025-12-24 @ 10:18 PM
Ignite Modification Date:
2025-12-25 @ 7:51 PM
Study NCT ID:
NCT03535935
Status:
UNKNOWN
Last Update Posted:
2020-12-07
First Post:
2018-05-13
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Efficacy, Safety and Response Predictors of Adjuvant Astragalus Therapy for Diabetic Kidney Disease
Sponsor:
The University of Hong Kong
Organization:
Study Overview
Official Title:
Efficacy, Safety and Response Predictors of Adjuvant Astragalus Therapy for Diabetic Kidney Disease (READY) - An Open-label Randomised Controlled Trial With Responder Regression Analysis
Status:
UNKNOWN
Status Verified Date:
2020-12
Last Known Status:
RECRUITING
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:
READY
Brief Summary:
This add-on open-label randomised controlled pragmatic trial aims to:
1. evaluate the effect of add-on astragalus treatment on type 2 diabetic patients with stage 2 to 3 chronic kidney disease and macroalbuminuria.
2. estimate treatment effect, variance, recruitment rate, attrition rate and change in clinical manifestation including Chinese medicine syndrome for parameters optimisation and feasibility assessment for a subsequent phase III randomised controlled trial.
3. assess response predictors for efficacy and safety among type 2 diabetic patients with stage 2 to 3 chronic kidney disease and macroalbuminuria receiving add-on astragalus treatment
1. evaluate the effect of add-on astragalus treatment on type 2 diabetic patients with stage 2 to 3 chronic kidney disease and macroalbuminuria.
2. estimate treatment effect, variance, recruitment rate, attrition rate and change in clinical manifestation including Chinese medicine syndrome for parameters optimisation and feasibility assessment for a subsequent phase III randomised controlled trial.
3. assess response predictors for efficacy and safety among type 2 diabetic patients with stage 2 to 3 chronic kidney disease and macroalbuminuria receiving add-on astragalus treatment
Detailed Description:
This add-on open-label randomised controlled pragmatic trial.
Sample size is calculated based on planned regression analysis. We believe an annual GFR benefit of 5 ml/min/1.73m2 is deemed significant clinically. 118 patients are therefore needed to offer a power of 70% to detect a GFR difference of 5 ml/min/1.73m2 over 48-week allowing 15% attrition rate for this study with a significance level of alpha equals to 0.05.
A trial management committee (TMC) formed by PA, Co-As and RA will centralise all the data of the trial. Co-As and RA will collect, clean and send the data of patients to TMC on a weekly basis. All data will be double entered to computer and cleaned before analysis to prevent data entry errors. All data transfer will be encrypted to protect patients' confidentiality. TMC will have regular meetings monthly with experts to discuss the progress of the trial. An independent Data Monitoring Board (DMB) will be invited to monitor the progress of the trial. DMB will advise ethics committee to terminate the trial if data is showing extreme benefits or harm. Detailed guidelines will be discussed and set by DMB.
Missing values will be imputed with last observation carried forward. Patient without a postrandomisation assessment for a particular efficacy endpoint will be excluded from the analysis of that endpoint.
Regression analysis will be used to compare the adjusted mean of eGFR, UACR, HbA1c, FBG, and other biomarkers at week 48 between groups and statistical significance. The adverse events will be analysed in a narrative manner. The percentage of all adverse events and the rate of attrition due to adverse events will be compared between intervention groups and control groups.
To minimise Type I error inflation, the analysis will follow a hierarchical approach in the order of 1) comparison of baseline to end of treatment on eGFR and UACR; 2) comparison of baseline to end of treatment on other outcome measurements; 3) comparison of baseline to treatment midpoints on eGFR and UACR and 4) comparison of baseline to treatment midpoints on other outcome measurements.
Subgroup analysis will be performed for different age groups, gender chronic kidney disease stage and severity of albuminuria.
The dependent variable is the treatment response which is categorised into:
1. Improved or stabilised renal function, defined as eGFR after 48-week treatment being higher or equal to baseline.
2. Non-responder, defined as patients having eGFR decreased at a rate of less than 5 mL/min/1.73m2 after 48-week treatment compared to baseline.
3. Rapid deteriorating renal function, defined as eGFR of more than 5 mL/min/1.73m2 after 48-week treatment compared to baseline.
Potential prognostic variables (baseline values) include:
1. Demographics and past medical history: Age, gender, body mass index (BMI), systolic blood pressure, history and duration of smoking and alcohol consumption and others
2. Chinese medicine diagnosis: presence of Chinese medicine syndromes (e.g. spleen and kidney qi deficiency) based on the presentation of standardised and commonly documented signs and symptoms
3. Biochemical profile
Sample size is calculated based on planned regression analysis. We believe an annual GFR benefit of 5 ml/min/1.73m2 is deemed significant clinically. 118 patients are therefore needed to offer a power of 70% to detect a GFR difference of 5 ml/min/1.73m2 over 48-week allowing 15% attrition rate for this study with a significance level of alpha equals to 0.05.
A trial management committee (TMC) formed by PA, Co-As and RA will centralise all the data of the trial. Co-As and RA will collect, clean and send the data of patients to TMC on a weekly basis. All data will be double entered to computer and cleaned before analysis to prevent data entry errors. All data transfer will be encrypted to protect patients' confidentiality. TMC will have regular meetings monthly with experts to discuss the progress of the trial. An independent Data Monitoring Board (DMB) will be invited to monitor the progress of the trial. DMB will advise ethics committee to terminate the trial if data is showing extreme benefits or harm. Detailed guidelines will be discussed and set by DMB.
Missing values will be imputed with last observation carried forward. Patient without a postrandomisation assessment for a particular efficacy endpoint will be excluded from the analysis of that endpoint.
Regression analysis will be used to compare the adjusted mean of eGFR, UACR, HbA1c, FBG, and other biomarkers at week 48 between groups and statistical significance. The adverse events will be analysed in a narrative manner. The percentage of all adverse events and the rate of attrition due to adverse events will be compared between intervention groups and control groups.
To minimise Type I error inflation, the analysis will follow a hierarchical approach in the order of 1) comparison of baseline to end of treatment on eGFR and UACR; 2) comparison of baseline to end of treatment on other outcome measurements; 3) comparison of baseline to treatment midpoints on eGFR and UACR and 4) comparison of baseline to treatment midpoints on other outcome measurements.
Subgroup analysis will be performed for different age groups, gender chronic kidney disease stage and severity of albuminuria.
The dependent variable is the treatment response which is categorised into:
1. Improved or stabilised renal function, defined as eGFR after 48-week treatment being higher or equal to baseline.
2. Non-responder, defined as patients having eGFR decreased at a rate of less than 5 mL/min/1.73m2 after 48-week treatment compared to baseline.
3. Rapid deteriorating renal function, defined as eGFR of more than 5 mL/min/1.73m2 after 48-week treatment compared to baseline.
Potential prognostic variables (baseline values) include:
1. Demographics and past medical history: Age, gender, body mass index (BMI), systolic blood pressure, history and duration of smoking and alcohol consumption and others
2. Chinese medicine diagnosis: presence of Chinese medicine syndromes (e.g. spleen and kidney qi deficiency) based on the presentation of standardised and commonly documented signs and symptoms
3. Biochemical profile
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: