Spironolactone Versus Spironolactone Plus Furosemide (SVSSF)

Overview

The question whether the sequential diuretic therapy, that means using an antialdosteronic drug at first and adding a loop diuretic in nonresponders, is better than the combination of the two diuretics from the beginning (combined diuretic therapy) in the treatment of ascites in patients with cirrhosis is still open. Therefore, the aim of the study is to compare sequential versus combined diuretic therapy in these patients. One hundred patients will be randomized into two groups. Group A will receive potassium canrenoate at the initial dose of 200 mg/day, then increased up to 400 mg/day. Non responders will be treated with 400 mg/day of potassium canrenoate and furosemide at an initial dose of 50 mg/day, then increased up to 150 mg/day. Group B will receive at first 200 mg/day of potassium canrenoate and 50 mg/day of furosemide, then increased up to 400 mg/day and 150 mg/day, respectively. The percentage of responders to dthe diuretic treatment, the time to get the resolution of ascites and the rate of adverse effects will be compared between the two Groups of Patients.

Full Title of Study: “Phase 4 Study on the Comparison Between Combined Versus Sequential Diuretic Treatment of Moderate Ascites in Nonazotemic Patients With Cirrhosis”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Treatment
  • Masking: None (Open Label)
• Study Primary Completion Date: September 2008

Interventions

• Drug: Spironolactone and furosemide
  • Patients in arm A will receive potassium canrenoate at the initial dose of 200 mg/day, then increased up to 400 mg/day. Non responders will be treated with 400 mg/day of potassium canrenoate and furosemide at an initial dose of 50 mg/day, then increased up to 150 mg/day.
• Drug: Spironolactone and furosemide
  • Patients in arm B will receive at first 200 mg/day of potassium canrenoate and 50 mg/day of furosemide, then increased up to 400 mg/day and 150 mg/day, respectively.

Arms, Groups and Cohorts

• Active Comparator: A
• Experimental: B

Clinical Trial Outcome Measures

Primary Measures

• the percentage of responders to the diuretic treatment; the percentage of patients who develop adverse effects to diuretics
  • Time Frame: within three weeks
• the percentage of patients who will respond to the diuretic treatment, the percentage of patients who will develop adverse effects to diuretics
  • Time Frame: within three weeks

Secondary Measures

• time to get the response to diuretics
  • Time Frame: within three weeks

Participating in This Clinical Trial

Inclusion Criteria

• Grade 2 ascites – Serum creatinine less than 1.2 mtg/dl – Serum sodium > 130 mmol/l – Serum potassium within 3.5 and 4.5 mmol/l – At least five days after the withdrawal of diuretics – A 90 mmol/day Na diet. Exclusion Criteria:

• Any therapeutic paracentesis for ascites before inclusion – Cardiac or respiratory disease – Gastrointestinal bleeding, hepatic encephalopathy, bacterial infections in the last 4 weeks before inclusion. – The use of NSAIDs or other nephrotoxic drugs in the last 4 weeks before inclusion.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • University of Padova
• Provider of Information About this Clinical Study
  • Prof. Paolo Angeli, Dept. of Clinical and Experimental Medicine

Citations Reporting on Results

Santos J, Planas R, Pardo A, Durandez R, Cabre E, Morillas RM, Granada ML, Jimenez JA, Quintero E, Gassull MA. Spironolactone alone or in combination with furosemide in the treatment of moderate ascites in nonazotemic cirrhosis. A randomized comparative study of efficacy and safety. J Hepatol. 2003 Aug;39(2):187-92. doi: 10.1016/s0168-8278(03)00188-0.