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

NCT ID: NCT03720067

Last Updated: 2019-05-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2/PHASE3

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-25

Study Completion Date

2022-12-20

Brief Summary

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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.

Detailed Description

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Conditions

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Cirrhosis Portal Hypertension Variceal Hemorrhage

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Phase 1: Propranolol (PPL)

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.

Group Type ACTIVE_COMPARATOR

Propranolol

Intervention Type DRUG

40mg to 320mg / day

Phase 1: Carvedilol (CVD)

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.

Group Type ACTIVE_COMPARATOR

Carvedilol

Intervention Type DRUG

6.25mg to 25mg / day

Phase 2: PPL non-responders/rosuvastatin

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.

Group Type ACTIVE_COMPARATOR

Propranolol

Intervention Type DRUG

40mg to 320mg / day

Rosuvastatin

Intervention Type DRUG

20mg / day

Phase 2: PPL non-responders/placebo

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.

Group Type PLACEBO_COMPARATOR

Propranolol

Intervention Type DRUG

40mg to 320mg / day

Placebo

Intervention Type DRUG

Placebo of rosuvastatin

Phase 2: CVD non-responders/rosuvastatin

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.

Group Type ACTIVE_COMPARATOR

Carvedilol

Intervention Type DRUG

6.25mg to 25mg / day

Rosuvastatin

Intervention Type DRUG

20mg / day

Phase 2: CVD non-responders/placebo

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.

Group Type PLACEBO_COMPARATOR

Carvedilol

Intervention Type DRUG

6.25mg to 25mg / day

Placebo

Intervention Type DRUG

Placebo of rosuvastatin

Interventions

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Propranolol

40mg to 320mg / day

Intervention Type DRUG

Carvedilol

6.25mg to 25mg / day

Intervention Type DRUG

Rosuvastatin

20mg / day

Intervention Type DRUG

Placebo

Placebo of rosuvastatin

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Universidade Federal do Rio de Janeiro

OTHER

Sponsor Role lead

Responsible Party

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Guilherme Rezende

Associated Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Universidade Federal do Rio de Janeiro

Rio de Janeiro, , Brazil

Site Status RECRUITING

Countries

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Brazil

Central Contacts

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Guilherme FM Rezende, MD, PhD

Role: CONTACT

(5521)999976292

Andre Luiz M Torres, MD

Role: CONTACT

(5521)998588246

Facility Contacts

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Guilherme FM Rezende, MD, PhD

Role: primary

55-21-999976292

Other Identifiers

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83211318.1.0000.5257

Identifier Type: -

Identifier Source: org_study_id

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