Eplerenone and spironolactone in male patients with ascites due to liver cirrhosis. A Swedish prospective randomized multicenter study of efficacy and endocrinologic side effects.

INTERVENTION: Trade Name: Spironolakton 50 mg and 100 mg Product Name: Spironolakton Pharmaceutical Form: Tablet Other descriptive name: SPIRONOLACTONE Trade Name: Inspra 25 mg and 50 mg Product Name: Inspra Pharmaceutical Form: Tablet Other descriptive name: EPLERENONE CONDITION: Ascites complicating liver cirrhosis in males ; MedDRA version: 14.1 Level: LLT Classification code 10024667 Term: Liver cirrhosis System Organ Class: 100000004871 ; MedDRA version: 14.1 Level: LLT Classification code 10021038 Term: Hyponatremia System Organ Class: 100000004861 ; MedDRA version: 14.1 Level: PT Classification code 10018800 Term: Gynaecomastia System Organ Class: 10038604 ‐ Reproductive system and breast disorders ; MedDRA version: 14.1 Level: LLT Classification code 10003146 Term: Arterial blood pressure decreased System Organ Class: 100000004848 ; MedDRA version: 14.1 Level: LLT Classification code 10040409 Term: Serum testosterone System Organ Class: 100000004848 ; MedDRA version: 15.1 Level: LLT Classification code 10025522 Term: Male sexual dysfunction NEC System Organ Class: 10038604 ‐ Reproductive system and breast disorders ; MedDRA version: 14.1 Level: LLT Classification code 10025503 Term: Male erectile disorder System Organ Class: 10038604 ‐ Reproductive system and breast disorders ; MedDRA version: 14.1 Level: LLT Classification code 10064704 Term: Decompensated cirrhosis System Organ Class: 100000004871 ; MedDRA version: 14.1 Level: LLT Classification code 10023422 Term: Kidney function abnormal System Organ Class: 100000004857 ; MedDRA version: 14.1 Level: LLT Classification code 10020647 Term: Hyperkalemia System Organ Class: 100000004861 ; MedDRA version: 14.1 Level: PT Classification code 10003445 Term: Ascites System Organ Class: 10017947 ‐ Gastrointestinal disorders Therapeutic area: Diseases [C] ‐ Digestive System Diseases [C06] PRIMARY OUTCOME: Main Objective: To evaluate if therapy with eplerenone is non‐inferior to spironolactone (both in combination with furosemide) regarding efficacy for mobilisation of ascites in male patients with cirrhosis of the liver. Primary end point(s): 1. Absence of clinically detectable ascites.; 2. Reduced clinical ascites with stable body weight +/‐ 1 kg from study week 12. Secondary Objective: To evaluate if therapy with eplerenone ‐ in doses which control ascites ‐ is superior to spironolactone (both in combination with furosemide) regarding antiandrogenic side effects (gynaecomastia, erectile dysfunction,reduced sexual arousal/desire, sex‐related quality of life).; Timepoint(s) of evaluation of this end point: 1. Study week 24; 2. Study week 24 SECONDARY OUTCOME: Secondary end point(s): 1. Absence or reduction of clinical ascites at week 12 ; 2. Prevalence of refractory ascites at week 24 (defined according to international criteria – ref) ; 3. Alteration of breast tenderness > 1 degree from start of treatment to week 24 ; 4. Alteration of gynaecomastia > 2 cm from start of treatment to week 24 ; 5. Difference in score for sexual dysfunction from start of treatment to week 24 ; 6. Difference in score for sexual dysfunction from start of treatment to week 24 ; 7. Difference in score for sex‐related QoL from start of treatment to week 24 ; 8. Differences in serum hormoneconcentrations from start of treatment to week 24 ; Timepoint(s) of evaluation of this end point: 1. Study week 12 ; 2 ‐ 8. Study week 24 INCLUSION CRITERIA: 1. A written informed consent to participate in the study is signed before any study‐related procedures are performed. 2. Male subject aged > 18 years and < 70 years 3. A definitive diagnosis of cirrhosis of the liver with clinically demonstrable ascites 4. A difference between plasma albumin concentration and ascites albumin concentration of > 10 g/liter Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) no F.1.2.1 Number of subjects for this age range 120 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30