Cirrhosis, Portal Hypertension, Variceal Hemorrhage
Conditions
Brief summary
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.
Interventions
DRUGPropranolol
40mg to 320mg / day
DRUGCarvedilol
6.25mg to 25mg / day
DRUGRosuvastatin
20mg / day
DRUGPlacebo
Placebo of rosuvastatin
Sponsors
Universidade Federal do Rio de Janeiro
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acute hemodynamic response | Two hours after a load dose of carvedilol or propranolol | A decrease in HVPG to 12 mmHg or lower |
| Full hemodynamic response to beta blockers | Eight weeks of carvedilol or propranolol | A decrease in HVPG to 12 mmHg or lower |
| Full hemodynamic response to beta blockers plus rosuvastatin or placebo | Eight weeks of beta blockers plus rosuvastatin or placebo | A decrease in HVPG to 12 mmHg or lower |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sufficient hemodynamic response to beta blockers plus rosuvastatin or placebo | Eight weeks of beta blockers plus rosuvastatin or placebo | A decrease in HVPG of at least 20% from baseline |
| Partial hemodynamic response to beta blockers plus rosuvastatin or placebo | Eight weeks of beta blockers plus rosuvastatin or placebo | A decrease in HVPG of at least 10% from baseline |
Countries
Brazil
Contacts
Primary ContactGuilherme FM Rezende, MD, PhD
Backup ContactAndre Luiz M Torres, MD
Outcome results
None listed