PCR: ARIA (Atacand Renoprotection In NephropAthy Pt.)

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00573430
• Collaborator: (none)
• Enrollment: 128
• Location: 1
• Arms: 3
• Duration (Months): 20
• Patients Per Site Per Month: 6.4

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Non-diabetic Nephropathy With Hypertension	Drug: Candesartan Cilexetil; Drug: Candesartan Cilexetil; Drug: Candesartan Cilexetil 32mg	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 128 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 28-week, Randomised, Open-label, Parallel-Group, Multi-Center Study To Find the Effective Dose of Candesartan Cilexetil (Atacand) for Renoprotection in Korean Hypertensive Patients With Non-diabetic Nephropathy
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Candesartan Cilexetil	Drug: Candesartan Cilexetil; 8 mg oral once daily dose; Other Names: Atacand
Experimental: 2 Candesartan Cilexetil	Drug: Candesartan Cilexetil; 16 mg oral once daily dose; Other Names: Atacand
Experimental: 3 Candesartan Cilexetil	Drug: Candesartan Cilexetil 32mg; 32 mg oral once daily dose; Other Names: Atacand

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Change of Systolic and Diastolic Blood Pressure From Baseline [baseline to 28 weeks]

2. Inflammatory Marker (Hs-C-peptide Reactive Protein) [baseline to 28 weeks]

   To evaluate how to reduce and relate with cardiovascular risk

3. 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)

4. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Seoul		Korea, Republic of

Sponsors and Collaborators

• AstraZeneca

Investigators

• Principal Investigator: Da Suk Han, Severance Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00573430
• Other Study ID Numbers: D2452L00015
• First Posted: Dec 14, 2007
• Last Update Posted: Aug 23, 2011
• Last Verified: Aug 1, 2011

• Keywords provided by AstraZeneca: Candesartan Cilexetil; Non-diabetic Nephropathy; hypertension; urine protein creatinine ratio
• Additional relevant MeSH terms: Kidney Diseases; Hypertension; Candesartan; Candesartan cilexetil

Study Results

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 Detail	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.

Arm/Group Title	Candesartan 8 mg	Candesartan 16mg	Candesartan 32mg
Arm/Group Description	Candesartan 8 mg oral once daily dose	Candesartan 16mg oral once daily dose	Candesartan 32mg oral once daily dose
Period Title: Overall Study
STARTED	40	45	43
COMPLETED	39	40	33
NOT COMPLETED	1	5	10

Baseline Characteristics

Arm/Group Title	Candesartan 8 mg	Candesartan 16mg	Candesartan 32mg	Total
Arm/Group Description	Candesartan 8 mg oral once daily dose	Candesartan 16mg oral once daily dose	Candesartan 32mg oral once daily dose	Total of all reporting groups
Overall Participants	40	45	43	128
Age (years) [Mean (Standard Deviation) ]
19 to 70	45.70 (11)	46.80 (16)	49.50 (11)	47.3 (13.4)
Gender (Number) [Number]
Female	20 50%	16 35.6%	17 39.5%	53 41.4%
Male	19 47.5%	28 62.2%	19 44.2%	66 51.6%

Outcome Measures

1. Primary Outcome

Title	The Change in Urinary Protein/Creatinine Ratio From Baseline to 28 Weeks
Description	Decrease of urinary protein/creatinine ratio means improvement of renal disease.
Time Frame	baseline to 28 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Candesartan 8 mg	Candesartan 16mg	Candesartan 32mg
Arm/Group Description	Candesartan 8 mg oral once daily dose	Candesartan 16mg oral once daily dose	Candesartan 32mg oral once daily dose
Measure Participants	39	44	36
Mean (Standard Deviation) [mg/g]	794.0 (1,070.10)	639.9 (863.30)	819.0 (823.60)

2. Secondary Outcome

Title	Change of Systolic and Diastolic Blood Pressure From Baseline
Time Frame	baseline to 28 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Candesartan 8 mg	Candesartan 16mg	Candesartan 32mg
Arm/Group Description	Candesartan 8 mg oral once daily dose	Candesartan 16mg oral once daily dose	Candesartan 32mg oral once daily dose
Measure Participants	39	44	36
Systolic	-11.70 (14.90)	-13.30 (14.90)	-16.10 (17.30)
Diastolic	-8.90 (13.30)	-8.00 (13.30)	-13.00 (14.70)

3. Secondary Outcome

Title	Inflammatory Marker (Hs-C-peptide Reactive Protein)
Description	To evaluate how to reduce and relate with cardiovascular risk
Time Frame	baseline to 28 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Candesartan 8 mg	Candesartan 16mg	Candesartan 32mg
Arm/Group Description	Candesartan 8 mg oral once daily dose	Candesartan 16mg oral once daily dose	Candesartan 32mg oral once daily dose
Measure Participants	38	41	35
Mean (Standard Deviation) [mg/dL]	0.01 (0.12)	-0.17 (1.86)	-0.01 (0.38)

4. Secondary Outcome

Title	Estimated GFR Predicted From the Modification of Diet in Renal Disease (MDRD) Equation
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Candesartan 8 mg	Candesartan 16mg	Candesartan 32mg
Arm/Group Description	Candesartan 8 mg oral once daily dose	Candesartan 16mg oral once daily dose	Candesartan 32mg oral once daily dose
Measure Participants	39	44	36
Mean (Standard Deviation) [mL/min/1.73 m2]	1.28 (8.45)	1.20 (9.31)	0.56 (8.92)

5. Secondary Outcome

Title	Treatment-emergent Adverse Events
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Candesartan 8 mg	Candesartan 16mg	Candesartan 32mg
Arm/Group Description	Candesartan 8 mg oral once daily dose	Candesartan 16mg oral once daily dose	Candesartan 32mg oral once daily dose
Measure Participants	40	43	47
Number [Participants]	28 70%	27 60%	25 58.1%

Adverse Events

Arm/Group Title	Candesartan 8 mg		Candesartan 16mg		Candesartan 32mg
Arm/Group Description	Candesartan 8 mg oral once daily dose		Candesartan 16mg oral once daily dose		Candesartan 32mg oral once daily dose
All Cause Mortality
	Candesartan 8 mg		Candesartan 16mg		Candesartan 32mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Candesartan 8 mg		Candesartan 16mg		Candesartan 32mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		1/45 (2.2%)		1/43 (2.3%)
Blood and lymphatic system disorders
Acute leukaemia	0/40 (0%)		0/45 (0%)		1/43 (2.3%)
Infections and infestations
Pnuemonia	0/40 (0%)		0/45 (0%)		1/43 (2.3%)
Nervous system disorders
dizziness	0/40 (0%)		1/45 (2.2%)		0/43 (0%)
Other (Not Including Serious) Adverse Events
	Candesartan 8 mg		Candesartan 16mg		Candesartan 32mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/40 (27.5%)		6/45 (13.3%)		9/43 (20.9%)
Infections and infestations
Nasopharyngitis	4/40 (10%)		2/45 (4.4%)		5/43 (11.6%)
Nervous system disorders
Dizziness	2/40 (5%)		2/45 (4.4%)		3/43 (7%)
Headache	2/40 (5%)		2/45 (4.4%)		0/43 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	3/40 (7.5%)		0/45 (0%)		1/43 (2.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.