Last updated on February 2018

Clinical Trial of HuangKui Capsule to Treat Diabetic Kidney Disease


Brief description of study

  1. Name of Investigational Products Huangkui capsule.
  2. Trial Topic A Randomized, Double-blinded, Parallel, controlled, Multicenter Clinical Trial of Huangkui Capsule in Treating Type II Diabetic Nephropathy (DKD)
  3. Trial Objectives Primary objective:To evaluate HuangKui capsule efficacy for treatment of type II diabetes ACR.
     Secondary objective: To evaluate the efficacy of HuangKui capsule on 24-hour urinary
     protein changesreduce PCR-increase eGFR, improve micro-inflammatory state, and
     improving Traditional Chinese medicine clinical efficacy

4. Trial Design Designed as a block randomized, double-blinded, parallel controlled, multi-center clinical trial.

Detailed Study Description

  1. Name of Investigational Products Huangkui capsule
  2. Trial Topic A Randomized, Double-blinded, Parallel, controlled, Multicenter Clinical Trial ofHuangkui Capsule in Treating Type II Diabetic Nephropathy (DKD)
  3. Trial Objectives Primary objective: To evaluate HuangKui capsule efficacy for treatment of type II diabetes ACR.
     Secondary objective: To evaluate the efficacy of HuangKui capsule on 24-hour urinary
     protein changesreduce PCR-increase eGFR, improve micro-inflammatory state, and
     improving Traditional Chinese medicine clinical efficacy.

4. Trial Design Designed as a block randomized, double-blinded, parallel controlled,

     multi-center clinical tria 4.1 Multi-center: The trial is proposed to be conducted in
     the department of Nephrology or Endocrinology of nine hospitals simultaneously.

     4.2 Randomization:Using stratified block randomized design. The randomization numbers
     were generated with SAS statistical software.

     4.3 Arms: The study subjects were divided into 3 arms: Huangkui arm, controlled arm and
     combined treatment arm.

     4.4 Estimation of subject numbers

     This study was based on the main indicator ACR to calculate the sample size, according
     to the clinical protocol:

     The change of ACR of Irbesartan combined with Huangkui capsule is superior than
     Irbesartan monotherapy.

     The changes of ACR in the monotherapy group were significantly lower than those in the
     irbesartan monotherapy group According to the experience of clinical treatment, it was
     found that the change of ACR was about 12.85mg / g before treatment with Irbesartan
     combined with Huangkui capsule group and 6.50mg / g before and after treatment with
     Irbesartan group, and  = 0.05 (bilateral (1-) = 80%, the standard deviation of the
     change value before and after ACR treatment with irbesartan combined with Huangkui
     capsule group was 17.18, Check the sample size calculation formula The number of samples
     in each group was calculated as n western medicine group = n combined treatment group =
     110 cases.

     Another group based on the clinical treatment experience to take the standard deviation
     of 17.18, take  = 0.025 (unilateral test),  = 0.2, that is, the degree of control
     (1-) = 80% of the case, the non-inferior boundary value of 6.50mg / g, according to the
     non-inferior test sample size calculation formula, The number of samples in each group
     was calculated as n western medicine group = n Chinese traditional treatment group = 110
     cases.According to the program requirements, the three groups were designed to be 1: 1:
     1, taking into account the blanding method and 20% rejection rate. ultimately a total of
     414 cases included in the case, each group of 138 cases.

     4.5 Blinding: double-blinding. Blinding will be conducted by statisticians as two levels
     of blinding. Level 1 Blinding: blinding of the investigational products. The
     investigational products and comparative products use unified packaging; level 2
     blinding: the blinding of the packaging box of investigational products.

5. Diagnostic criteria The etiology of Diabetic nephropathy is kidney damage, referred to

     DN in the past (diabetic nephropathy). But in 2007, the American Foundation for Kidney
     Disease (NKF) developed guidelines for the life quality of kidney disease (NKF / KDOQI).
     The guidelines recommend that DKD (diabetic kidney disease) instead of DN. In 2014, the
     American Diabetes Association (ADA) and NKF reached a consensus that DKD referred to the
     chronic kidney disease caused by diabetes, including glomerular filtration rate (GFR)
     which is less than 60ml.min-1.1.73m-2 or urine white Protein / creatinine ratio (ACR) is
     higher than 30 mg / g for more than 3 months,associated with diabetic retinopathy.

     During having diagnosis, if one of the following circumstances happened, we should
     consider its CKD is caused by (1) no diabetic retinopathy; (2) GFR lower or decreased
     rapidly; (3) a sharp increase in proteinuria or nephrotic syndrome; (4) refractory
     hypertension; (5) urinary sediment activity;(6) symptoms or signs of other systemic
     diseases; (7) glomerular filtration rate decreased by more than 30% within 2-3 months
     after initiation of treatment with angiotensin converting enzyme inhibitors (ACEI) or
     angiotensin II receptor antagonists (ARB).

     5.2 Table of TCM symptom/signs Diagnostic dosage It is refer to "Clinical research
     guidelines of new drug of Traditional Chinese Medicine "(2002 version), which published
     by China Medical Science andTechnology Press

6. Treatment options 6.1 Basic treatment 6.1.1 Anti-hypotensive We can choose

     antihypertensive drugs Monotherapy or combined controling blood pressure expect ACEI and
     ARB, control blood pressure in 160 / 90mmHg the following 6.1.2 Anti-hypoglycemic We can
     use oral hypoglycemic agents or insulin for hypoglycemic, so that glycosylated
     hemoglobin  8.5%.

     6.1.3 Anti-hypolipidemic We can choose to use statins or fibrates lipid-lowering drugs.
     6.1.4 Diet control Patients with edema should limit the salt and water, daily sodium
     intake <5g; high protein diet increased glomerular hyperperfusion, high filtration, and
     therefore advocated the principle of high quality low-protein diet. Protein intake
     should be a high biological value of animal protein-based, early protein intake should
     be limited to 1g/kgd 6.2 Investigational products Huangkui Capsule: produced by SZYY
     Group Pharmaceutical Limited, Jiangsu, 0.5g30 capsules/box Placebo that simulates
     Huangkui capsule: produced by SZYY Group Pharmaceutical Limited, 0.5g30 capsules/box
     Irbesartan tablets: produced by Sanofi (Hangzhou) Pharmaceutical Co., Ltd., 150mg7
     capsules/box Placebo that simulates Irbesartan tablets: produced by SZYY Group
     Pharmaceutical Limited, Jiangsu, 150mg7 capsules/box 6.3 Trial process 6.3.1 Treatment
     for observation period The subjects who meet the inclusion criteria will be randomized
     into three groups at a 1:1:1 ratio.

     Test group: Placebo drug that simulates Irbesartan tablets 150mg /qd, oral dose;
     Huangkui Capsule 2.5g/tid, oral dose.

     Control group: irbesartan tablets 150mg /qd, oral dose; Placebo drug that simulates
     Huangkui capsule 2.5g/tid, oral dose.

     Combined treatment group: irbesartan tablets 150mg /qd, oral dose; Huangkui Capsule
     2.5g/tid, oral dose.

     6.3.2 period of treatment Treatment observation period is 24 weeks, follow-up points:
     Week 0, 4, 8, 12, 16, 20, 24.

     6.4 Concomitant medications During the import period and throughout the treatment, do
     not use the RAS blockers (ARB or ACEI) other than the investigational product irbesartan
     and Potassium-sparing diuretics, Calcium dobesilate, Aldehyde-containing starch, or
     other Chinese medicine which can reduce proteinuria.

     If other medicines have been used before the trial, the subjects can continue to use
     them. The use of these medicines should be recorded.

     6.5 ACR Detection Specimens: one - time morning urine (after 5:00); Urinary creatinine
     detection method: enzyme kinetics; urinary albumin detection method : immune
     turbidimetric method. 6.6 PCR detection Specimens: 24h urine Urine creatinine detection
     method: Enzyme kinetic method Urine protein detection method: dye binding method PCR =
     urinary protein / creatinine

7. Efficacy endpoint 7.1 Efficacy endpoint 7.1.1 Primary endpoints ACR baseline changes and

     changes in the rate 7.1.2 Secondary endpoints 124-hour urinary protein quantification
     baseline changes and changes in the rate 2PCR baseline changes and changing rate
     3Glomerular filtration rate (eGFR)baseline changes 4High sensitivity C - reactive
     protein baseline values 5TCM syndromes Efficacy endpoint Changes and the rate change
     before and after treatment. [Time point: baseline,12-weeks treatment,24-weeks treatment]

     7.2 Efficacy endpoint Evaluation endpoints 7.2.1 The ACR change rate ( refer to "Guiding
     principles of clinical research on the treatment of chronic nephritis with traditional
     Chinese medicine", 2002 version; The State Administration of Traditional Chinese
     Medicine in 1987 to develop the Efficacy endpoint of chronic glomerulonephritis standard
     ) Complete remission: ACR is less than 30mg/g; Markedly effective: ACR decreased more
     than 50% before treatment Effective: ACR decreased more than 30%-50% before treatment
     Invalid: those who did not meet these targets. 7.2.2 Efficacy endpoint for TCM syndrome
     Changes in value and rate before and after treatment before and after treatment [Time
     point: baseline,12-weeks treatment,24-weeks treatment]

8. Safety Evaluation endpoints 8.1 Vital signs, such as such as body temperature, pulse, breathing, blood pressure and so on.

     8.2 Blood, urine routine test, liver function test(ALBALTAST), renal function
     test(BunSCr, UAeGFR), electrocardiogram, blood potassium, blood sugar; Adverse
     events/adverse reactions.

9. Statistical Methods All statistical calculations were carried out using SAS v9.3

     statistical analysis software, hypothesis testing are used bilateral test, unless
     otherwise specified, the overall comparison between the test level = 0.05.

Statistical analysis includesThree groups of subjects enrolled No., drop out and excluded cases, demographic and other baseline characteristics, compliance, efficacy analysis and safety analysis.

For quantitative data, we conduct descriptive statistical analysis with cases, averages, standard deviation, minimum, median, maximum, upper quartile (Q1), lower quartile (Q3) and 95% confidence interval (95% CI). Comparisons between treatment groups were performed using either an analysis of variance or a Wilcoxon rank sum test. If the influence of covariates is taken into account, a general linear model (GLM) is used.

Descriptive statistical analysis of qualitative data is given in terms of the number of cases and their percentages. Count data were compared between each treatment group, using x2 test, Fisher exact probability method; grade data in each treatment group or between groups before and after treatment comparison analysis, Wilcoxon rank sum test. If the effects of the center or other factors are taken into account, a CMH x2 test or Logistic regression is used.

Clinical Study Identifier: NCT03016832

Contact Investigators or Research Sites near you

Start Over

Wei Sun

Jiangsu Province Hospital of TCM
Nanjing, China
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Recruitment Status: Open


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