Shiga Microalbuminuria Reduction Trial-2

• Sponsor: Shiga University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01461499
• Collaborator: (none)
• Enrollment: 237
• Location: 1
• Arms: 2
• Duration (Months): 38
• Patients Per Site Per Month: 6.2

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the effects of a direct renin inhibitor (DRI), aliskiren, on the urinary albumin excretion in hypertensive patients with type 2 diabetes under strict blood pressure control with angiotensin receptor blocker (ARB).

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus; Hypertension	Drug: Aliskiren; Drug: any angiotensin receptor blockers	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 237 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clinical Investigation on the Effects of Reducing Microalbuminuria in Hypertensive Patients With Type 2 Diabetes - SMART2
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Aug 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Direct renin inhibitor	Drug: Aliskiren; The patient will start taking one a daily 150 mg/day of aliskiren. In case blood pressure doesn't reach the target (SBP/DBP < 130/80 mmHg), higher dose of aliskiren will be given.In case the blood pressure doesn't achieve the target, another anti-hypertensive drug other than RAS inhibitors (ARB or ACE-inhibitor) or potassium-retaining diuretics will be added from the minimum effective dose.
Active Comparator: Angiotensin receptor blockers	Drug: any angiotensin receptor blockers; The patient will start taking one a standard dose of an ARB in Japan. In case blood pressure doesn't reach the target (SBP/DBP < 130/80 mmHg), higher dose of the ARB will be given. In case the blood pressure doesn't achieve the target, another anti-hypertensive drug other than RAS inhibitors (DRI, another ARB or ACE-inhibitor) or potassium-retaining diuretics will be added from the minimum effective dose.

Outcome Measures

Primary Outcome Measures

1. Reduction in Albuminuria [baseline and 24 weeks]

   Change in the urinary albumin to creatinine ratio (UACR) from the baseline

Secondary Outcome Measures

1. Change in the Urinary Angiotensinogen Level [baseline and 24 weeks]

   Change in the urinaryurinary angiotensinogen level from the baseline

2. Change in the Plasma Renin Activity [baseline and 24 weeks]

3. Change in the Serum Insulin Level [baseline and 24 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Segment: outpatients

• Hypertension: taking an anti-hypertensive treatment or indicating mean sitting SBP/DBP more than130/80 mmHg

• Type 2 diabetes: diagnosed by ADA criteria or under an anti-diabetic drug treatment

• Microalbuminuria: 10 < and < 300 mg/gCr

• Informed consent: patients who understand well about this study based on own voluntary will and can give a written consent

Exclusion Criteria:

• Sever hypertension (over 180/110 mmHg), malignant hypertension and secondary hypertension

• Type 1 diabetes

• Patients whose investigator regards as difficult to comply with study protocol in reference to the package insert of aliskiren

• Patients who have history of operation in gastrointestinal tract surgery, and anamnestic or concurrent gastrointestinal disorders, which may interfere with drug absorption

• Serum potassium > 5.6 mEq/L (hyperkalemia)

• Urinary microalbumin < 10 or > 300 mg/gCr

• Patients who participated in another clinical study within three months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Shiga University of Medical Science	Otsu	Shiga	Japan	520-2192

Sponsors and Collaborators

• Shiga University

Investigators

• Study Chair: Hiroshi Maegawa, M.D., Shiga University of Medical Science

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hiroshi Maegawa, Professor of Medicine, Shiga University
• ClinicalTrials.gov Identifier: NCT01461499
• Other Study ID Numbers: SMART-2
• First Posted: Oct 28, 2011
• Last Update Posted: Feb 19, 2018
• Last Verified: Aug 1, 2017

• Keywords provided by Hiroshi Maegawa, Professor of Medicine, Shiga University: Hypertension; Albuminuria; Direct renin inhibitor; Angiotensin receptor blocker; Type 2 diabetes
• Additional relevant MeSH terms: Hypertension; Diabetes Mellitus, Type 2; Angiotensin Receptor Antagonists

Study Results

Participant Flow

Arm/Group Title	Direct Renin Inhibitor	Angiotensin Receptor Blockers
Arm/Group Description	Aliskiren: A total of 119 patients were randomly assigned to receive direct renin inhibitor. Eight patients dropped out during the observation period and a total of 111 patients were studied in this group.	A total of 118 patients were randomly assigned to receive angiotensin receptor blockers. Four patients dropped out during the observation period and a total of 114 patients were studied in this group.
Period Title: Overall Study
STARTED	119	118
COMPLETED	111	114
NOT COMPLETED	8	4

Baseline Characteristics

Arm/Group Title	Direct Renin Inhibitor	Angiotensin Receptor Blockers	Total
Arm/Group Description	Aliskiren: The patient will start taking one a daily 150 mg/day of aliskiren. In case blood pressure doesn't reach the target (SBP/DBP < 130/80 mmHg), higher dose of aliskiren will be given.In case the blood pressure doesn't achieve the target, another anti-hypertensive drug other than RAS inhibitors (ARB or ACE-inhibitor) or potassium-retaining diuretics will be added from the minimum effective dose.	any angiotensin receptor blockers: The patient will start taking one a standard dose of an ARB in Japan. In case blood pressure doesn't reach the target (SBP/DBP < 130/80 mmHg), higher dose of the ARB will be given. In case the blood pressure doesn't achieve the target, another anti-hypertensive drug other than RAS inhibitors (DRI, another ARB or ACE-inhibitor) or potassium-retaining diuretics will be added from the minimum effective dose.	Total of all reporting groups
Overall Participants	111	114	225
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	55 49.5%	57 50%	112 49.8%
>=65 years	56 50.5%	57 50%	113 50.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.9 (9.3)	63.0 (8.4)	63.0 (8.8)
Sex: Female, Male (Count of Participants)
Female	34 30.6%	33 28.9%	67 29.8%
Male	77 69.4%	81 71.1%	158 70.2%
Region of Enrollment (participants) [Number]
Japan	111 100%	114 100%	225 100%

Outcome Measures

1. Primary Outcome

Title	Reduction in Albuminuria
Description	Change in the urinary albumin to creatinine ratio (UACR) from the baseline
Time Frame	baseline and 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Direct Renin Inhibitor	Angiotensin Receptor Blockers
Arm/Group Description	Aliskiren: The patient will start taking one a daily 150 mg/day of aliskiren. In case blood pressure doesn't reach the target (SBP/DBP < 130/80 mmHg), higher dose of aliskiren will be given.In case the blood pressure doesn't achieve the target, another anti-hypertensive drug other than RAS inhibitors (ARB or ACE-inhibitor) or potassium-retaining diuretics will be added from the minimum effective dose. A total of 378 patients were enrolled for screening, and 141 were not meeting inclusion criteria. Thus, 237 were randomly assigned to receive either direct renin inhibitor (119) or angiotensin receptor blockers (118). Eight patients dropped out during the observation period and a total of 111 patients were studied in this group.	any angiotensin receptor blockers: The patient will start taking one a standard dose of an ARB in Japan. In case blood pressure doesn't reach the target (SBP/DBP < 130/80 mmHg), higher dose of the ARB will be given. In case the blood pressure doesn't achieve the target, another anti-hypertensive drug other than RAS inhibitors (DRI, another ARB or ACE-inhibitor) or potassium-retaining diuretics will be added from the minimum effective dose. A total of 378 patients were enrolled for screening, and 141 were not meeting inclusion criteria. Thus, 237 were randomly assigned to receive either direct renin inhibitor (119) or angiotensin receptor blockers (118). Four patients dropped out during the observation period and a total of 114 patients were studied in this group.
Measure Participants	111	114
Mean (95% Confidence Interval) [percentage of UACR change]	-5.5	-6.7

2. Secondary Outcome

Title	Change in the Urinary Angiotensinogen Level
Description	Change in the urinaryurinary angiotensinogen level from the baseline
Time Frame	baseline and 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Direct Renin Inhibitor	Angiotensin Receptor Blockers
Arm/Group Description	Aliskiren: A total of 378 patients were enrolled for screening, and 141 were not meeting inclusion criteria. Thus, 237 were randomly assigned to receive either direct renin inhibitor (119) or angiotensin receptor blockers (118). Eight patients dropped out during the observation period and a total of 111 patients were studied in this group.	Angiotensin receptor blockers: A total of 378 patients were enrolled for screening, and 141 were not meeting inclusion criteria. Thus, 237 were randomly assigned to receive either direct renin inhibitor (119) or angiotensin receptor blockers (118). Four patients dropped out during the observation period and a total of 114 patients were studied in this group.
Measure Participants	111	114
Mean (95% Confidence Interval) [percentage of change UATGCR]	-1.7	-5.4

3. Secondary Outcome

Title	Change in the Plasma Renin Activity
Time Frame	baseline and 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Change in the Serum Insulin Level
Time Frame	baseline and 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Direct Renin Inhibitor		Angiotensin Receptor Blockers
Arm/Group Description	Aliskiren: The patient will start taking one a daily 150 mg/day of aliskiren. In case blood pressure doesn't reach the target (SBP/DBP < 130/80 mmHg), higher dose of aliskiren will be given.In case the blood pressure doesn't achieve the target, another anti-hypertensive drug other than RAS inhibitors (ARB or ACE-inhibitor) or potassium-retaining diuretics will be added from the minimum effective dose. 378 patients were enrolled for screening, and 237 were randomly assigned to receive either direct renin inhibitor (119) or angiotensin receptor blockers (118). Eight patients dropped out during the observation period and a total of 111 patients were studied in this group.		any angiotensin receptor blockers: The patient will start taking one a standard dose of an ARB in Japan. In case blood pressure doesn't reach the target (SBP/DBP < 130/80 mmHg), higher dose of the ARB will be given. In case the blood pressure doesn't achieve the target, another anti-hypertensive drug other than RAS inhibitors (DRI, another ARB or ACE-inhibitor) or potassium-retaining diuretics will be added from the minimum effective dose. 378 patients were enrolled for screening, and 237 were randomly assigned to receive either direct renin inhibitor (119) or angiotensin receptor blockers (118). Four patients dropped out during the observation period and a total of 114 patients were studied in this group.
All Cause Mortality
	Direct Renin Inhibitor		Angiotensin Receptor Blockers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/119 (0%)		0/118 (0%)
Serious Adverse Events
	Direct Renin Inhibitor		Angiotensin Receptor Blockers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/119 (0%)		0/118 (0%)
Other (Not Including Serious) Adverse Events
	Direct Renin Inhibitor		Angiotensin Receptor Blockers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/119 (1.7%)		2/118 (1.7%)
Infections and infestations
pneumonia	2/119 (1.7%)	5	2/118 (1.7%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.