UMIN-CTR Clinical Trial

Public title

The efficacy of tolvaptan in a population with congestive heart failure and chronic kidney disease: A multicenter, randomized, open label, blind endpoint study (AQUAKID-Study)

Acronym

The efficacy of tolvaptan in a population with congestive heart failure and chronic kidney disease

Scientific Title

The efficacy of tolvaptan in a population with congestive heart failure and chronic kidney disease: A multicenter, randomized, open label, blind endpoint study (AQUAKID-Study)

Scientific Title:Acronym

The efficacy of tolvaptan in a population with congestive heart failure and chronic kidney disease

Region

Japan

Condition

congestive heart failure and chronic kidney disease

Classification by specialty

Cardiology

Nephrology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To investigate the clinical efficacy of tolvaptan in patients with congestive heart failure (CHF) and chronic kidney disease (CKD) in comparison with furosemide as an active control. In an acute-phase trial, we investigate the impact of CKD on the clinical effectiveness of tolvaptan therapy for CHF with CKD. In the long-term follow up, we investigate whether tolvaptan decelerates the progress of CKD.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Phase IV

Primary outcomes

1.acute-phase trial
Absolute change of body weight, rate of increase/decrease of body weight.
Development of acute kidney injury on CKD
Bioelectrical impedance analysis: Extracellular water, intracellular water, and total body water

2.long term follow up study
Delta estimated glomerular filtration rate (eGFR), 50% decrease in eGFR
Composite outcome: 50% decrease in eGFR+induction of renal replacement therapy

Key secondary outcomes

1.acute-phase trial
Renal function tests:serum creatinine, eGFR, urine osmolality, and urine 24-hour Na excretion
Neurohumoral factors:plasma renin activity, serum aldosterone, and plasma catecholamine fraction, plasma midkine level, urine angiotensinogen level, urine midkine level, N-terminal prohormone of brain natriuretic peptide, arginine vasopressin, and urine aquaporin-2
Dose of diuretics converted for furosemide
Other concomitant drugs for treating CHF: atrial natriuretic peptides, phosphodiesterase III inhibitors, catecholamines, and colforsins
Health related QOL indicators (SF-36)
Induction of renal replacement therapy
Length of initial hospitalization

2.long-term follow-up study
Absolute change in body weight and rate of change
Health-related QOL indicator measured by using the SF-36
Cardiac echocardiography imaging
Re-hospitalization for CHF
Direct cost of medical expenditure from claim data
Cardiovascular events
Total mortality

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -but assessor(s) are blinded

Control

Active

Stratification

NO

Dynamic allocation

YES

Institution consideration

Institution is not considered as adjustment factor.

Blocking

NO

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

1. acute-phase trial
Start treatment with 15 mg tolvaptan with concomitant use of diuretics prescribed for the initial assessment period of 15 days.

2. long-term follow-up study
Patients who tolerate tolvaptan will continue the treatment for the next 2 years.

Interventions/Control_2

1. acute-phase trial
Start treatment with 40 mg furosemide with concomitant use of diuretics prescribed for the initial assessment period of 15 days.

2. long term follow up study
Patients who tolerate furosemide will continue the treatment for the next 2 years.

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1. Irrespective of the route of administration, the patients are prescribed diuretics equivalent to a dose of furosemide between 20-240 mg/day, and the diuretic dose was not changed between day 1 and day 2
2. Patients satisfying the criteria of GFR <60 ml/min/1.73m2 or urine protein of >=0.50 g/gCr (g/day) or urine protein >=2+ assessed by using test tape
3. Patients satisfying the Framingham criteria for CHF

Key exclusion criteria

1. Patients who recently started undergoing hemodialysis
2. Patients treated with the following drugs during the initial eligibility assessment period
(a) Phosphodiesterase III inhibitors (amrinone, milinone, or loprinone)
(b) Catecholamines
(c) Colforsins
3. Acute renal failure
4. Hypernatremia, Na levels &#8805;147 mEq/dL
5. Patients unable to sense thirst or those with difficulty drinking water
6. Anuria
7. Patients with malignancy, including multiple myeloma or primary amyloidosis
8. Patients suspected of having loss of circulating plasma volume or patients with hypotension
9. Severe aortic stenosis or severe dilated cardiomyopathy
10. Acute coronary syndrome
11. Recent myocardial infarction, percutaneous coronary intervention (PCI), or coronary artery bypass graft (CABG) within the past 3 months
12. Patients scheduled for PCI or CABG
13. Stroke within the past 3 months
14. Severe neuropsychological deficit
15. Severe liver damage or hepatic coma
16. Severe obstructive and/or restrictive lung disease
17. Severe pulmonary hypertension
18. Patients with other life-threatening illnesses
19. Pregnant women
20. Allergy to tolvaptan
21. Others deemed ineligible for this trial by physicians

Target sample size

100

Name of lead principal investigator

1st name
Middle name
Last name	Yukio Yuzawa

Organization

Fujita Health University School of Medicine

Division name

Department of Nephrology

Zip code

Address

1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi Pref., Japan

TEL

0562-93-9345

Email

hhayashi@fujita-hu.ac.jp

Name of contact person

1st name
Middle name
Last name	Hiroki Hayashi

Organization

Fujita Health University School of Medicine

Division name

Department of Nephrology

Zip code

Address

1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi Pref., Japan

TEL

0562-93-9345

Homepage URL

Email

hhayashi@fujita-hu.ac.jp

Institute

Fujita Health University School of Medicine

Institute

Department

Personal name

Organization

The Kidney Foundation, Aichi

Organization

Division

Category of Funding Organization

Non profit foundation

Nationality of Funding Organization

Japan

Co-sponsor

Chita City Hospital, Okazaki City Hospital, TOYOTA Memorial Hospital, Tono Kosei Hospital

Name of secondary funder(s)

Fujita Health University Clinical Research Grant

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2013

Year

10

Month

09

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

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

Recruitment status

Enrolling by invitation

Date of protocol fixation

2013

Year

01

Month

01

Day

Date of IRB

Anticipated trial start date

2013

Year

02

Month

01

Day

Last follow-up date

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2013

Year

10

Month

09

Day

Last modified on

2014

Year

04

Month

16

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000014031