UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000001003
Receipt number R000001210
Scientific Title A randomized trial of the beta-adrenergic antagonist carvedilol in chronic kidney disease
Date of disclosure of the study information 2008/02/22
Last modified on 2008/01/31 17:41:27

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Basic information

Public title

A randomized trial of the beta-adrenergic antagonist carvedilol in chronic kidney
disease

Acronym

CArvedilol REnoprotective CKD trial: CARE-CKD trial

Scientific Title

A randomized trial of the beta-adrenergic antagonist carvedilol in chronic kidney
disease

Scientific Title:Acronym

CArvedilol REnoprotective CKD trial: CARE-CKD trial

Region

Japan


Condition

Condition

Chronic kidney disease at stage of 3, 4 and 5

Classification by specialty

Nephrology

Classification by malignancy

Others

Genomic information

NO


Objectives

Narrative objectives1

To ask whether patients with CKD stage 3, 4 and 5 may obtain more renoprotection with an add-on of carvedilol on the top of standard CKD treatment.

Basic objectives2

Efficacy

Basic objectives -Others


Trial characteristics_1

Exploratory

Trial characteristics_2

Explanatory

Developmental phase

Phase III


Assessment

Primary outcomes

A combined renal outcome of a doubling of serum creatinine concentration and/or end-stage renal disease

Key secondary outcomes

1) estimated glomerular filtration rate
2) dairy proteinuria excretion
3) blood pressure, heart rate
4) cardiovascular events
5) cardiac ultrasound
6) blood neurohormones, hANP, and BNP levels


Base

Study type

Interventional


Study design

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -but assessor(s) are blinded

Control

Placebo

Stratification

YES

Dynamic allocation

YES

Institution consideration

Institution is not considered as adjustment factor.

Blocking

YES

Concealment

Numbered container method


Intervention

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Eligible patients with CKD stage 3, 4 and 5 were enrolled in a parallel, open-label, placebo controlled, randomized treatment protocol. During a run-in phase of about one month, all patients received 1.25 mg of carvedilol two times a day in order to determine which patients were unable to tolerate low doses of carvedilol.
The patients were requested to visit their doctors every two weeks for their medical checks. Patients who could not tolerate such a dose were excluded from this trial. Remaining patients were then randomly assigned to receive either placebo or carvedilol by 1:1 stratified randomization. They continued their background treatment for renoprotection. During the titration period, the dose of carvedilol was doubled at one-month interval and then increased to a target dose of 10 mg twice a day. When the dose increase was not tolerated for the appearance of adverse reactions such as symptomatic fatigue, HR <50 beats/min or arterial hypotension (BP <90/60 mm Hg), it was temporarily halved, then again increased at same interval. The final dose of carvedilol was individually titrated. At the end of the up-titration phase, the therapy with carvedilol or placebo was maintained to the end of this study of three years. Antihypertensive agents with dihydropyridine calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists and others was maintained, although the dosage was adjusted according to the clinical conditions of the patient or to the appearance of side effects possibly related to these drugs. First agent to consider was dihydropyridine calcium channel blockers, while the RAAS blockers were last agent to adjust. A total experimental period was 2.5 years.

Interventions/Control_2

The same protocol was followed for patients allocated to the placebo group.

Interventions/Control_3


Interventions/Control_4


Interventions/Control_5


Interventions/Control_6


Interventions/Control_7


Interventions/Control_8


Interventions/Control_9


Interventions/Control_10



Eligibility

Age-lower limit

18 years-old <=

Age-upper limit

70 years-old >=

Gender

Male and Female

Key inclusion criteria

Age 18 - 70 years, chronic kidney disease stage 3, 4 and 5, as defined by the Japanese Society of Nephrology (JSN), standard renoprotective treatment recommended by the JSN committee, their physical status and laboratory results maintained with variation of less than 30% during at least three consecutive measurements, for a minimum of 3 months after the first consultation, without evidence of urinary-tract infection or overt heart failure (New York Heart Association [NYHA] class III-IV) and acute cardiovascular acidents; and no history of allergic reaction to drugs, especially beta-adrenergic antagonists.

Key exclusion criteria

Exclusion criteria were: immediate need for renal replacement therapy; treatment-resistant oedema; need for treatment with corticosteroids, non-steroidal anti-inflammatory drugs, or immunosuppressive drugs; proteinuria greater than 10 g per day and hypoalbuminaemia less than 28 g/L (normal range 36&#8211;50 g/L); renovascular hypertension; malignant hypertension, myocardial infarction, or cerebrovascular accident in the year preceding the trial; severe peripheral vascular disease; severe congestive heart failure (NYHA III&#8211;IV); chronic hepatic disease (rise of serum aminotransferase concentration); connective-tissue disease; obstructive uropathy; cancer; chronic pulmonary disease; drug or alcohol misuse; pregnancy; and breastfeeding.

Target sample size

200


Research contact person

Name of lead principal investigator

1st name
Middle name
Last name Naoyuki Nakao

Organization

Rokko Island Hospital

Division name

Division of Nephrology

Zip code


Address

KoYo-cho naka 2-11, Higashinada, kobe

TEL

078-858-1111

Email



Public contact

Name of contact person

1st name
Middle name
Last name Naoyuki Nakao

Organization

Rokko Island Hospital

Division name

Division of Nephrology

Zip code


Address

KoYoCho naka 2-11 Higashinada Kobe Hyogo Japan

TEL

078-858-1111

Homepage URL


Email



Sponsor or person

Institute

Rokko Island Hospital-Clinical Research Committee

Institute

Department

Personal name



Funding Source

Organization

None

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization



Other related organizations

Co-sponsor

None

Name of secondary funder(s)

None


IRB Contact (For public release)

Organization


Address


Tel


Email



Secondary IDs

Secondary IDs

NO

Study ID_1


Org. issuing International ID_1


Study ID_2


Org. issuing International ID_2


IND to MHLW



Institutions

Institutions



Other administrative information

Date of disclosure of the study information

2008 Year 02 Month 22 Day


Related information

URL releasing protocol


Publication of results

Partially published


Result

URL related to results and publications


Number of participants that the trial has enrolled


Results

Renoprotective efficacy of carvedilol, presented at theAnnual scientific meeting of American Society of nephrology in 2007 (SA-FC039).

Results date posted


Results Delayed


Results Delay Reason


Date of the first journal publication of results


Baseline Characteristics


Participant flow


Adverse events


Outcome measures


Plan to share IPD


IPD sharing Plan description



Progress

Recruitment status

Completed

Date of protocol fixation

1995 Year 04 Month 19 Day

Date of IRB


Anticipated trial start date

1995 Year 05 Month 01 Day

Last follow-up date

2007 Year 11 Month 01 Day

Date of closure to data entry

2008 Year 02 Month 01 Day

Date trial data considered complete

2008 Year 02 Month 01 Day

Date analysis concluded

2008 Year 05 Month 01 Day


Other

Other related information



Management information

Registered date

2008 Year 01 Month 31 Day

Last modified on

2008 Year 01 Month 31 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000001210


Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name