Propranolol, Carvedilol and Rosuvastatin in the Prevention of Variceal Bleeding in Cirrhotic Portal Hypertension (Betastatin)
Cirrhosis, Portal Hypertension, Variceal Hemorrhage
About this trial
This is an interventional treatment trial for Cirrhosis
Eligibility Criteria
Inclusion Criteria:
- Hepatic cirrhosis of any etiology
- Previous variceal bleeding
- Endoscopic variceal eradication at least 2 weeks before
Exclusion Criteria:
- Beta blocker or statin contraindications
- Model for End-Stage Liver Disease (MELD) score > 25
- Child-Pugh score > 13
- HVPG ≤ 12 mmHg
- Creatinine clearance < 50 mL/min
- Refractory ascites
- Hepatic encephalopathy stages 3 or 4
- Alcohol use in the last 6 months
- Hepatitis C treatment in the last 6 months
- Changing or initiating a new hepatitis B treatment in the last 6 months
- Malignant neoplasms from any origin except basal cell carcinoma
- HIV infection
- Pregnancy
- Anticoagulation
- Recent or complete portal vein thrombosis
Sites / Locations
- Universidade Federal do Rio de JaneiroRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Active Comparator
Active Comparator
Active Comparator
Placebo Comparator
Active Comparator
Placebo Comparator
Phase 1: Propranolol (PPL)
Phase 1: Carvedilol (CVD)
Phase 2: PPL non-responders/rosuvastatin
Phase 2: PPL non-responders/placebo
Phase 2: CVD non-responders/rosuvastatin
Phase 2: CVD non-responders/placebo
Hepatic venous pressure gradient (HVPG) will be measured before and after 120 minutes of a loading dose of Propranolol (PPL) 80 mg PO. Thereafter, patients will receive maintenance therapy with Propranolol (40 to 320 mg / day) adjusted according to blood pressure and heart rate. After 28 days of reaching the maximum tolerated dose, a new HVPG measurement will be performed.
HVPG will be measured before and after 120 minutes of a loading dose of Carvedilol (CVD) 12.5 mg PO. Thereafter, patients will receive maintenance therapy with Carvedilol (6.25 - 25 mg / day) adjusted according to blood pressure. After 28 days of reaching the maximum tolerated dose, a new HVPG measurement will be performed.
Patients treated with PROPRANOLOL (PPL) who do not reach HVPG fall below 12 mmHg will be randomized to receive the addition of ROSUVASTATIN 20 mg /day PO. HVPG will be measured again after 56 days.
Patients treated with PROPRANOLOL (PPL) who do not reach HVPG fall below 12 mmHg will be randomized to receive the addition of PLACEBO 1 tablet PO. HVPG will be measured again after 56 days.
Patients treated with CARVEDILOL (CVD) who do not reach HVPG fall below 12 mmHg will be randomized to receive the addition of ROSUVASTATIN 20 mg /day PO. HVPG will be measured again after 56 days.
Patients treated with CARVEDILOL (CVD) who do not reach HVPG fall below 12 mmHg will be randomized to receive the addition of PLACEBO 1 tablet PO. HVPG will be measured again after 56 days.