Propranolol, Carvedilol and Rosuvastatin in the Prevention of Variceal Bleeding in Cirrhotic Portal Hypertension (Betastatin)

Universidade Federal do Rio de Janeiro

Status and phase: Unknown; Phase 3; Phase 2

Conditions: Portal Hypertension; Cirrhosis; Variceal Hemorrhage

Treatments: Drug: Carvedilol; Drug: Rosuvastatin; Drug: Propranolol; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT03720067

83211318.1.0000.5257

Details and patient eligibility

About

Patients with hepatic cirrhosis and previous variceal bleeding will be randomly assigned to use propranolol or carvedilol. After 8 weeks, rosuvastatin or placebo will be blindly added to nonresponders (HVPG measurement > 12mmHg) for another 8 weeks and hemodynamic response will be assessed again.

Surrogate serum markers of portal hypertension will be evaluated and correlated to HVPG values and to its variations.

Enrollment: 80 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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80 participants in 6 patient groups, including a placebo group

Phase 1: Propranolol (PPL)

Active Comparator group

Description:

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.

Treatment:

Drug: Propranolol

Phase 1: Carvedilol (CVD)

Active Comparator group

Description:

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.

Treatment:

Drug: Carvedilol

Phase 2: PPL non-responders/rosuvastatin

Active Comparator group

Description:

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.

Treatment:

Drug: Propranolol

Drug: Rosuvastatin

Phase 2: PPL non-responders/placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Propranolol

Drug: Placebo

Phase 2: CVD non-responders/rosuvastatin

Active Comparator group

Description:

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.

Treatment:

Drug: Carvedilol

Drug: Rosuvastatin

Phase 2: CVD non-responders/placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Drug: Carvedilol