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

UMIN ID: UMIN000001003

Registered date:22/02/2008

Basic Information

• Recruitment status: Complete: follow-up complete
• Health condition(s) or Problem(s) studied: Chronic kidney disease at stage of 3, 4 and 5
• Date of first enrollment: 1995/05/01
• Target sample size: 200
• Countries of recruitment: Japan
• Study type: Interventional

Intervention(s)

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

Outcome(s)

• Primary Outcome: A combined renal outcome of a doubling of serum creatinine concentration and/or end-stage renal disease
• Secondary Outcome: 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

Key inclusion & exclusion criteria

• Age minimum: 18years-old
• Age maximum: 70years-old
• Gender: Male and Female
• Exclude 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 36–50 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–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.

Related Information

• Primary Sponsor: Rokko Island Hospital-Clinical Research Committee
• Secondary Sponsor: None
• Source(s) of Monetary Support: None,None