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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1: Propranolol (PPL) | Active Comparator | 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. |
|
| Phase 1: Carvedilol (CVD) | Active Comparator | 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. |
|
| Phase 2: PPL non-responders/rosuvastatin | Active Comparator | 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. |
|
| Phase 2: PPL non-responders/placebo | Placebo Comparator | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Propranolol | Drug | 40mg to 320mg / day |
|
| Measure | Description | Time Frame |
|---|---|---|
| Acute hemodynamic response | A decrease in HVPG to 12 mmHg or lower | Two hours after a load dose of carvedilol or propranolol |
| Full hemodynamic response to beta blockers | A decrease in HVPG to 12 mmHg or lower | Eight weeks of carvedilol or propranolol |
| Full hemodynamic response to beta blockers plus rosuvastatin or placebo | A decrease in HVPG to 12 mmHg or lower | Eight weeks of beta blockers plus rosuvastatin or placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Sufficient hemodynamic response to beta blockers plus rosuvastatin or placebo | A decrease in HVPG of at least 20% from baseline | Eight weeks of beta blockers plus rosuvastatin or placebo |
| Partial hemodynamic response to beta blockers plus rosuvastatin or placebo |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Guilherme FM Rezende, MD, PhD | Contact | (5521)999976292 | guimottarezende@gmail.com | |
| Andre Luiz M Torres, MD | Contact | (5521)998588246 | torres.alm@gmail.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Universidade Federal do Rio de Janeiro | Recruiting | Rio de Janeiro | Brazil |
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| Phase 2: CVD non-responders/rosuvastatin | Active Comparator | 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. |
|
| Phase 2: CVD non-responders/placebo | Placebo Comparator | 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. |
|
| Carvedilol | Drug | 6.25mg to 25mg / day |
|
| Rosuvastatin | Drug | 20mg / day |
|
| Placebo | Drug | Placebo of rosuvastatin |
|
A decrease in HVPG of at least 10% from baseline |
| Eight weeks of beta blockers plus rosuvastatin or placebo |
| ID | Term |
|---|---|
| D005355 | Fibrosis |
| D006975 | Hypertension, Portal |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D011433 | Propranolol |
| D000077261 | Carvedilol |
| D000068718 | Rosuvastatin Calcium |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D002227 | Carbazoles |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D006575 | Heterocyclic Compounds, 3-Ring |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D005464 | Fluorobenzenes |
| D006845 | Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
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