Spironolactone Versus Spironolactone Plus Furosemide (SVSSF) (SVSSF)

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

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.

Study Overview

• Status: Completed
• Conditions: Cirrhosis; Ascites
• Intervention / Treatment: Drug: Spironolactone and furosemide; Drug: Spironolactone and furosemide

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Padova, Italy, 35100
    • University of Padova, Dept. of Clinical and Experimental Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A	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.
Experimental: B	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
the percentage of responders to the diuretic treatment; the percentage of patients who develop adverse effects to diuretics	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	within three weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
time to get the response to diuretics	within three weeks

Collaborators and Investigators

• Sponsor: University of Padova

Publications and helpful links

General Publications

• 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.
• Angeli P, Fasolato S, Mazza E, Okolicsanyi L, Maresio G, Velo E, Galioto A, Salinas F, D'Aquino M, Sticca A, Gatta A. Combined versus sequential diuretic treatment of ascites in non-azotaemic patients with cirrhosis: results of an open randomised clinical trial. Gut. 2010 Jan;59(1):98-104. doi: 10.1136/gut.2008.176495.

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: August 22, 2008
• First Submitted That Met QC Criteria: August 25, 2008
• First Posted (Estimate): August 26, 2008

Study Record Updates

• Last Update Posted (Estimate): September 25, 2008
• Last Update Submitted That Met QC Criteria: September 24, 2008
• Last Verified: September 1, 2008

More Information

Terms related to this study

• Keywords: furosemide; cirrhosis; hyperkalemia; nitric oxide; ascites; plasma renin activity; diuretic therapy; potassium canrenoate; serum sodium concentration; refractory ascites; Nonazotemic patients with cirrhosis and moderate ascites
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis; Ascites; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Sodium Potassium Chloride Symporter Inhibitors; Spironolactone; Furosemide
• Other Study ID Numbers: 318P