Propranolol, Carvedilol and Rosuvastatin in the Prevention of Variceal Bleeding in Cirrhotic Portal Hypertension
Betastatin
1 other identifier
interventional
80
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jan 2019
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 23, 2018
CompletedFirst Posted
Study publicly available on registry
October 25, 2018
CompletedStudy Start
First participant enrolled
January 25, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 20, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
December 20, 2022
CompletedMay 14, 2019
May 1, 2019
1.9 years
October 23, 2018
May 12, 2019
Conditions
Outcome Measures
Primary Outcomes (3)
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
Secondary Outcomes (2)
Sufficient hemodynamic response to beta blockers plus rosuvastatin or placebo
Eight weeks of beta blockers plus rosuvastatin or placebo
Partial hemodynamic response to beta blockers plus rosuvastatin or placebo
Eight weeks of beta blockers plus rosuvastatin or placebo
Study Arms (6)
Phase 1: Propranolol (PPL)
ACTIVE COMPARATORHepatic 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 COMPARATORHVPG 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 COMPARATORPatients 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 COMPARATORPatients 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.
Phase 2: CVD non-responders/rosuvastatin
ACTIVE COMPARATORPatients 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 COMPARATORPatients 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.
Interventions
40mg to 320mg / day
6.25mg to 25mg / day
20mg / day
Placebo of rosuvastatin
Eligibility Criteria
You may qualify if:
- Hepatic cirrhosis of any etiology
- Previous variceal bleeding
- Endoscopic variceal eradication at least 2 weeks before
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Universidade Federal do Rio de Janeiro
Rio de Janeiro, Brazil
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Associated Professor
Study Record Dates
First Submitted
October 23, 2018
First Posted
October 25, 2018
Study Start
January 25, 2019
Primary Completion
December 20, 2020
Study Completion
December 20, 2022
Last Updated
May 14, 2019
Record last verified: 2019-05
Data Sharing
- IPD Sharing
- Will not share