search
Back to results

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

Primary Purpose

Cirrhosis, Portal Hypertension, Variceal Hemorrhage

Status
Unknown status
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Propranolol
Carvedilol
Rosuvastatin
Placebo
Sponsored by
Universidade Federal do Rio de Janeiro
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cirrhosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Universidade Federal do Rio de JaneiroRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Active Comparator

Active Comparator

Active Comparator

Placebo Comparator

Active Comparator

Placebo Comparator

Arm Label

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

Arm 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.

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.

Outcomes

Primary Outcome Measures

Acute hemodynamic response
A decrease in HVPG to 12 mmHg or lower
Full hemodynamic response to beta blockers
A decrease in HVPG to 12 mmHg or lower
Full hemodynamic response to beta blockers plus rosuvastatin or placebo
A decrease in HVPG to 12 mmHg or lower

Secondary Outcome Measures

Sufficient hemodynamic response to 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
A decrease in HVPG of at least 10% from baseline

Full Information

First Posted
October 23, 2018
Last Updated
May 12, 2019
Sponsor
Universidade Federal do Rio de Janeiro
search

1. Study Identification

Unique Protocol Identification Number
NCT03720067
Brief Title
Propranolol, Carvedilol and Rosuvastatin in the Prevention of Variceal Bleeding in Cirrhotic Portal Hypertension
Acronym
Betastatin
Official Title
Propranolol, Carvedilol and Rosuvastatin in the Prevention of Recurrent Variceal Haemorrhage in Patients With Cirrhotic Portal Hypertension
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Unknown status
Study Start Date
January 25, 2019 (Actual)
Primary Completion Date
December 20, 2020 (Anticipated)
Study Completion Date
December 20, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Universidade Federal do Rio de Janeiro

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cirrhosis, Portal Hypertension, Variceal Hemorrhage

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase 1: Propranolol (PPL)
Arm Type
Active Comparator
Arm 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.
Arm Title
Phase 1: Carvedilol (CVD)
Arm Type
Active Comparator
Arm 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.
Arm Title
Phase 2: PPL non-responders/rosuvastatin
Arm Type
Active Comparator
Arm 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.
Arm Title
Phase 2: PPL non-responders/placebo
Arm Type
Placebo Comparator
Arm 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.
Arm Title
Phase 2: CVD non-responders/rosuvastatin
Arm Type
Active Comparator
Arm 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.
Arm Title
Phase 2: CVD non-responders/placebo
Arm Type
Placebo Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Propranolol
Intervention Description
40mg to 320mg / day
Intervention Type
Drug
Intervention Name(s)
Carvedilol
Intervention Description
6.25mg to 25mg / day
Intervention Type
Drug
Intervention Name(s)
Rosuvastatin
Intervention Description
20mg / day
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo of rosuvastatin
Primary Outcome Measure Information:
Title
Acute hemodynamic response
Description
A decrease in HVPG to 12 mmHg or lower
Time Frame
Two hours after a load dose of carvedilol or propranolol
Title
Full hemodynamic response to beta blockers
Description
A decrease in HVPG to 12 mmHg or lower
Time Frame
Eight weeks of carvedilol or propranolol
Title
Full hemodynamic response to beta blockers plus rosuvastatin or placebo
Description
A decrease in HVPG to 12 mmHg or lower
Time Frame
Eight weeks of beta blockers plus rosuvastatin or placebo
Secondary Outcome Measure Information:
Title
Sufficient hemodynamic response to beta blockers plus rosuvastatin or placebo
Description
A decrease in HVPG of at least 20% from baseline
Time Frame
Eight weeks of beta blockers plus rosuvastatin or placebo
Title
Partial hemodynamic response to beta blockers plus rosuvastatin or placebo
Description
A decrease in HVPG of at least 10% from baseline
Time Frame
Eight weeks of beta blockers plus rosuvastatin or placebo

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Guilherme FM Rezende, MD, PhD
Phone
(5521)999976292
Email
guimottarezende@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Andre Luiz M Torres, MD
Phone
(5521)998588246
Email
torres.alm@gmail.com
Facility Information:
Facility Name
Universidade Federal do Rio de Janeiro
City
Rio de Janeiro
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guilherme FM Rezende, MD, PhD
Phone
55-21-999976292
Email
guimottarezende@gmail.com
First Name & Middle Initial & Last Name & Degree
Andre Luiz M Torres, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs