Diabetic NephropathiesPhase 2/3READYNCT03535935
Efficacy, Safety and Response Predictors of Adjuvant Astragalus Therapy for Diabetic Kidney Disease
A Phase 2/3 study testing Astragalus Powder and Routine medical care (active comparator) in people with Diabetic Nephropathies and Diabetic Kidney Disease, run by The University of Hong Kong at 2 sites in Hong Kong.
Trial 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. Read more about this study
- Who is it for?
- Ages 35 to 80 years
- Conditions the study is for
- Diabetic Nephropathies, Diabetic Kidney Disease
- What is being tested?
- Astragalus Powder and Routine medical care (active comparator)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 118 participants
- Where
- 2 sitesHong Kong
- Study dates
- 1 Jul 2018to 31 Dec 2022
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- diagnosed with type 2 diabetes for at least 5 years;
- with an estimated glomerular filtration rate (GFR) ≥30 ˂90 mL/min/1.73m2 confirmed with repeat testing over three or more months calculated by the abbreviated MDRD study equation;
- persistent macroalbuminuria with spot urine albumin-to-creatinine ratio (UACR) ≥ 300 mg/g confirmed by at least 2 out of 3 consecutive first morning void urine samples;
- on stable dose of anti-diabetic drug including insulin for 12 weeks;
- on stable dose of angiotensin-converting-enzyme inhibitor or angiotensin receptor blocker for 12 weeks; and
- willing and able to give written informed consent
Who cannot join
- with known history of glomerulonephritis, polycystic kidney disease, systemic lupus erythematosus, any suggestive evidence of nondiabetic glomerulopathy;
- with known history of kidney transplant;
- with concurrent severe disorders of heart, brain, liver, and hematopoietic system, tumor and mental disorder;
- with deranged liver function;
- poorly controlled blood pressure;
- with known history of intolerance or malabsorption of oral medications;
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- with uncontrollable urinary infection;
- experiencing pregnancy; or
- participating in other clinical trial within 30 days
Trial locations and contacts
2 sites in 1 country.
Hong Kong2 sites, 2 recruiting
- Recruiting
Queen Mary Hospital
Hong Kong
Sydney CW TANG, MD, PhD, +852 22553879, scwtang@hku.hk
Kam Wa CHAN, BCM, MCM, MSc.(PH), +852 22553207, chriskwcchan@hku.hk
- Not yet recruiting
School of Chinese Medicine
Hong Kong
Lixing LAO, MD, PHD
About this study
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
This add-on open-label randomised controlled pragmatic trial aims to:
- evaluate the effect of add-on astragalus treatment on type 2 diabetic patients with stage 2 to 3 chronic kidney disease and macroalbuminuria.
- 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.
- 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
Read the 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:
- Improved or stabilised renal function, defined as eGFR after 48-week treatment being higher or equal to baseline.
- 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.
- 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:
- Demographics and past medical history: Age, gender, body mass index (BMI), systolic blood pressure, history and duration of smoking and alcohol consumption and others
- 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
- Biochemical profile
- Conditions
- Diabetic Nephropathies, Diabetic Kidney Disease
- Being tested
- Astragalus Powder, Routine medical care (active comparator)
- Keywords
- Chinese medicine, Astragalus, Pragmatic trial
- Medical subject headings
- Diabetic Nephropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Astragalus PowderDrug
3 grams of water soluble astragalus sachets (equivalent to 15g raw herbs) administrated orally on top of standard medical care for 48 weeks.
Patients will have 5 days of medicine per week and will be advised to take the medicine once daily dissolved in boiling water in the first 5 days of the week.
Routine medical care (active comparator)Other
Angiotensin converting enzyme inhibitor or angiotensin receptor blocker
| Study group | Role | What they receive |
|---|---|---|
| Standard medical care | Active comparator | Angiotensin converting enzyme inhibitor or angiotensin receptor blocker and oral hypoglycemic agents or insulin Receives: Other: Routine medical care (active comparator) |
| Add on astragalus powder | Experimental | 3 grams of water soluble astragalus sachets (equivalent to 15g raw herbs) administrated orally on top of standard medical care for 48 weeks. Receives: Drug: Astragalus Powder; Other: Routine medical care (active comparator) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in estimated GFR
Efficacy and safety
Measured: From baseline to 48 weeks after treatment
Change in spot urine albumin-to-creatinine ratio
Efficacy and safety
Measured: From baseline to 48 weeks after treatment
Secondary outcomes (4)
Change in glycated haemoglobin (HbA1c)
Measured: From baseline to 48 weeks after treatment
Change in urinary monocyte chemotactic protein 1 (MCP-1)
Measured: From baseline to 48 weeks after treatment
Change in urinary Cystatin C
Measured: From baseline to 48 weeks after treatment
Change in lipids
Measured: From baseline to 48 weeks after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2018
- Study start1 Jul 2018
- Primary completion30 Jun 2022 (estimated)
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Diabetic NephropathiesStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 118 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sydney CW TANG, The University of Hong Kong
- Investigators
- Sydney CW TANG, MD, PhD, Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03535935
- Sponsor's protocol ID
- RE-02
- Acronym
- READY
- Status last verified
- Dec 2020
- First submitted
- 13 May 2018
- Last updated
- 7 Dec 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Chan KW, Kwong ASK, Tsui PN, Chan GCW, Choi WF, Yiu WH, Cheung SCY, Wong MMY, Zhang ZJ, Tan KCB, Lao L, Lai KN, Tang SCW; READY and SCHEMATIC research group. Add-on astragalus in type 2 diabetes and chronic kidney disease: A multi-center, assessor-blind, randomized controlled trial. Phytomedicine. 2024 Jul 25;130:155457. doi: 10.1016/j.phymed.2024.155457. Epub 2024 Feb 28.
PubMed 38810556Chan KW, Kwong ASK, Tsui PN, Cheung SCY, Chan GCW, Choi WF, Yiu WH, Zhang Y, Wong MM, Zhang ZJ, Tan KCB, Lao L, Tang SCW. Efficacy, safety and response predictors of adjuvant astragalus for diabetic kidney disease (READY): study protocol of an add-on, assessor-blind, parallel, pragmatic randomised controlled trial. BMJ Open. 2021 Jan 12;11(1):e042686. doi: 10.1136/bmjopen-2020-042686.
PubMed 33436470
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03535935
- Acronym / sponsor ID
- READY / RE-02
- Conditions
- Diabetic Nephropathies, Diabetic Kidney Disease
- Keywords
- Chinese medicine, Astragalus, Pragmatic trial
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 118 participants (estimated)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Study start
- 1 Jul 2018 (actual)
- Primary completion
- 30 Jun 2022 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 24 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This add-on open-label randomised controlled pragmatic trial aims to:
- evaluate the effect of add-on astragalus treatment on type 2 diabetic patients with stage 2 to 3 chronic kidney disease and macroalbuminuria.
- 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.
- 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:
- Improved or stabilised renal function, defined as eGFR after 48-week treatment being higher or equal to baseline.
- 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.
- 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:
- Demographics and past medical history: Age, gender, body mass index (BMI), systolic blood pressure, history and duration of smoking and alcohol consumption and others
- 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
- Biochemical profile
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard medical care | Active comparator | Other: Routine medical care (active comparator)Angiotensin converting enzyme inhibitor or angiotensin receptor blocker and oral hypoglycemic agents or insulin |
| Add on astragalus powder | Experimental | Drug: Astragalus Powder, Other: Routine medical care (active comparator)3 grams of water soluble astragalus sachets (equivalent to 15g raw herbs) administrated orally on top of standard medical care for 48 weeks. |
Who may qualify
- Ages
- 35 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- diagnosed with type 2 diabetes for at least 5 years;
- with an estimated glomerular filtration rate (GFR) ≥30 ˂90 mL/min/1.73m2 confirmed with repeat testing over three or more months calculated by the abbreviated MDRD study equation;
- persistent macroalbuminuria with spot urine albumin-to-creatinine ratio (UACR) ≥ 300 mg/g confirmed by at least 2 out of 3 consecutive first morning void urine samples;
- on stable dose of anti-diabetic drug including insulin for 12 weeks;
- on stable dose of angiotensin-converting-enzyme inhibitor or angiotensin receptor blocker for 12 weeks; and
Key exclusion criteria (9 listed)
- with known history of glomerulonephritis, polycystic kidney disease, systemic lupus erythematosus, any suggestive evidence of nondiabetic glomerulopathy;
- with known history of kidney transplant;
- with concurrent severe disorders of heart, brain, liver, and hematopoietic system, tumor and mental disorder;
- with deranged liver function;
- poorly controlled blood pressure;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Astragalus Powder3 grams of water soluble astragalus sachets (equivalent to 15g raw herbs) administrated orally on top of standard medical care for 48 weeks. Patients will have 5 days of medicine per week and will be advised to take the medicine once daily dissolved in boiling water in the first 5 days of the week. | Drug | Add on astragalus powder |
| Routine medical care (active comparator)Angiotensin converting enzyme inhibitor or angiotensin receptor blocker | Other | Add on astragalus powder, Standard medical care |
Primary outcome
Change in estimated GFR
Time frame: From baseline to 48 weeks after treatment
Efficacy and safety
Change in spot urine albumin-to-creatinine ratio
Time frame: From baseline to 48 weeks after treatment
Efficacy and safety
4 secondary outcomes
Change in glycated haemoglobin (HbA1c)
Time frame: From baseline to 48 weeks after treatment
Change in urinary monocyte chemotactic protein 1 (MCP-1)
Time frame: From baseline to 48 weeks after treatment
Change in urinary Cystatin C
Time frame: From baseline to 48 weeks after treatment
Change in lipids
Time frame: From baseline to 48 weeks after treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2020.
- Derived from this study: PubMed 38810556Chan KW, Kwong ASK, Tsui PN, Chan GCW, Choi WF, Yiu WH, Cheung SCY, Wong MMY, Zhang ZJ, Tan KCB, Lao L, Lai KN, Tang SCW; READY and SCHEMATIC research group. Add-on astragalus in type 2 diabetes and chronic kidney disease: A multi-center, assessor-blind, randomized controlled trial. Phytomedicine. 2024 Jul 25;130:155457. doi: 10.1016/j.phymed.2024.155457. Epub 2024 Feb 28.
- Derived from this study: PubMed 33436470Chan KW, Kwong ASK, Tsui PN, Cheung SCY, Chan GCW, Choi WF, Yiu WH, Zhang Y, Wong MM, Zhang ZJ, Tan KCB, Lao L, Tang SCW. Efficacy, safety and response predictors of adjuvant astragalus for diabetic kidney disease (READY): study protocol of an add-on, assessor-blind, parallel, pragmatic randomised controlled trial. BMJ Open. 2021 Jan 12;11(1):e042686. doi: 10.1136/bmjopen-2020-042686.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sydney CW TANG, MD, PhD principal investigator
The University of Hong Kong
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Astragalus Powder and Routine medical care (active comparator) in people with Diabetic Nephropathies and Diabetic Kidney Disease, run by The University of Hong Kong at 2 sites in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sydney CW TANG, MD, PhD (+852 22553879, scwtang@hku.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in estimated GFR (time frame: From baseline to 48 weeks after treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03535935, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2020.