Non-diabetic Nephropathy With Hypertension
Conditions
Keywords
Candesartan Cilexetil, Non-diabetic Nephropathy, hypertension, urine protein creatinine ratio
Brief summary
To determine the effective dose of candesartan cilexetil for reduction of urinary protein excretion in hypertensive patients with non-diabetic chronic kidney disease with baseline urinary protein/creatinine ratio between 500mg/g and 5000mg/g, by assessing the change in urinary protein/creatinine ratio from baseline to the end of 28-week treatment
Interventions
DRUGCandesartan Cilexetil
8 mg oral once daily dose
32 mg oral once daily dose
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* hypertension; a)135mmHg \< Systolic Blood Pressure \<180mmHg and/or 85 mmHg \< Diastolic Blood Pressure \<100 mmHg. or b) The subject has been treated with antihypertensive medication * proteinuria (urinary protein/creatinine ratio between 500 mg/g and 5000 mg/g)
Exclusion criteria
* Current serum-creatinine \> 265 mmol/L (\>3 mg/dL). * Current serum-potassium \> 5.5 mmol/L * Known hypersensitivity to angiotensin (AT)1-receptor blocker
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Change in Urinary Protein/Creatinine Ratio From Baseline to 28 Weeks | baseline to 28 weeks | Decrease of urinary protein/creatinine ratio means improvement of renal disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Inflammatory Marker (Hs-C-peptide Reactive Protein) | baseline to 28 weeks | To evaluate how to reduce and relate with cardiovascular risk |
| Change of Systolic and Diastolic Blood Pressure From Baseline | baseline to 28 weeks | — |
| Estimated GFR Predicted From the Modification of Diet in Renal Disease (MDRD) Equation | 28 weeks | GFR (mL/min/1.73 m2) = 186 x (Scr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.210 if African-American) (conventional units) |
| Treatment-emergent Adverse Events | Baseline to 28 weeks | Prevalence of adverse events after treatment regardless causality. An adverse event is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition from the signing of the informed consent, whether or not considered causally related to the product. |
Countries
South Korea
Participant flow
Recruitment details
155 enrolled, 27 screening failure, 128 randomized. Eligibility criteria not fulfilled meant subjects who were not fulfilled at Visit 1 or Enrolment, but screening failure subjects were who fulfilled at Visit 1, but not at Visit 2 after screening period.
Pre-assignment details
Total 128 patient enrolled, but among of them, 9 subjects excluded from analysis because of Withdrawal by Subject, Protocol violation, Eligibility criteria not fullfiled. You can see these number in above table. This analysis was conducted based on Intend to treat. Therefore, total analyzed number is 119, and 39, 44, 36 per arm respectively.
Participants by arm
| Arm | Count |
|---|---|
| Candesartan 8 mg Candesartan 8 mg oral once daily dose | 40 |
| Candesartan 16mg Candesartan 16mg oral once daily dose | 45 |
| Candesartan 32mg Candesartan 32mg oral once daily dose | 43 |
| Total | 128 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 2 |
| Overall Study | Eligibility criteria not fulfilled | 0 | 0 | 3 |
| Overall Study | Incorrect enrollment of randomization | 0 | 4 | 3 |
| Overall Study | Protocol Violation | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Candesartan 8 mg | Candesartan 16mg | Candesartan 32mg | Total |
|---|---|---|---|---|
| Age Continuous 19 to 70 | 45.70 years STANDARD_DEVIATION 11 | 46.80 years STANDARD_DEVIATION 16 | 49.50 years STANDARD_DEVIATION 11 | 47.3 years STANDARD_DEVIATION 13.4 |
| Gender Female | 20 Participants | 16 Participants | 17 Participants | 53 Participants |
| Gender Male | 19 Participants | 28 Participants | 19 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 40 | 6 / 45 | 9 / 43 |
| serious Total, serious adverse events | 0 / 40 | 1 / 45 | 1 / 43 |
Outcome results
Primary
The Change in Urinary Protein/Creatinine Ratio From Baseline to 28 Weeks
Decrease of urinary protein/creatinine ratio means improvement of renal disease.
Time frame: baseline to 28 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Candesartan 8 mg | The Change in Urinary Protein/Creatinine Ratio From Baseline to 28 Weeks | 794.0 mg/g | — |
| Candesartan 16mg | The Change in Urinary Protein/Creatinine Ratio From Baseline to 28 Weeks | 639.9 mg/g | Standard Deviation 863.3 |
| Candesartan 32mg | The Change in Urinary Protein/Creatinine Ratio From Baseline to 28 Weeks | 819.0 mg/g | Standard Deviation 823.6 |
Secondary
Change of Systolic and Diastolic Blood Pressure From Baseline
Time frame: baseline to 28 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Candesartan 8 mg | Change of Systolic and Diastolic Blood Pressure From Baseline | Systolic | -11.70 mmHg | Standard Deviation 14.9 |
| Candesartan 8 mg | Change of Systolic and Diastolic Blood Pressure From Baseline | Diastolic | -8.90 mmHg | Standard Deviation 13.3 |
| Candesartan 16mg | Change of Systolic and Diastolic Blood Pressure From Baseline | Systolic | -13.30 mmHg | Standard Deviation 14.9 |
| Candesartan 16mg | Change of Systolic and Diastolic Blood Pressure From Baseline | Diastolic | -8.00 mmHg | Standard Deviation 13.3 |
| Candesartan 32mg | Change of Systolic and Diastolic Blood Pressure From Baseline | Systolic | -16.10 mmHg | Standard Deviation 17.3 |
| Candesartan 32mg | Change of Systolic and Diastolic Blood Pressure From Baseline | Diastolic | -13.00 mmHg | Standard Deviation 14.7 |
Secondary
Estimated GFR Predicted From the Modification of Diet in Renal Disease (MDRD) Equation
GFR (mL/min/1.73 m2) = 186 x (Scr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.210 if African-American) (conventional units)
Time frame: 28 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Candesartan 8 mg | Estimated GFR Predicted From the Modification of Diet in Renal Disease (MDRD) Equation | 1.28 mL/min/1.73 m2 | Standard Deviation 8.45 |
| Candesartan 16mg | Estimated GFR Predicted From the Modification of Diet in Renal Disease (MDRD) Equation | 1.20 mL/min/1.73 m2 | Standard Deviation 9.31 |
| Candesartan 32mg | Estimated GFR Predicted From the Modification of Diet in Renal Disease (MDRD) Equation | 0.56 mL/min/1.73 m2 | Standard Deviation 8.92 |
Secondary
Inflammatory Marker (Hs-C-peptide Reactive Protein)
To evaluate how to reduce and relate with cardiovascular risk
Time frame: baseline to 28 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Candesartan 8 mg | Inflammatory Marker (Hs-C-peptide Reactive Protein) | 0.01 mg/dL | Standard Deviation 0.12 |
| Candesartan 16mg | Inflammatory Marker (Hs-C-peptide Reactive Protein) | -0.17 mg/dL | Standard Deviation 1.86 |
| Candesartan 32mg | Inflammatory Marker (Hs-C-peptide Reactive Protein) | -0.01 mg/dL | Standard Deviation 0.38 |
Secondary
Treatment-emergent Adverse Events
Prevalence of adverse events after treatment regardless causality. An adverse event is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition from the signing of the informed consent, whether or not considered causally related to the product.
Time frame: Baseline to 28 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Candesartan 8 mg | Treatment-emergent Adverse Events | 28 Participants |
| Candesartan 16mg | Treatment-emergent Adverse Events | 27 Participants |
| Candesartan 32mg | Treatment-emergent Adverse Events | 25 Participants |