CirrhosisPhase 2/3BetastatinNCT03720067
Propranolol, Carvedilol and Rosuvastatin in the Prevention of Variceal Bleeding in Cirrhotic Portal Hypertension
A Phase 2/3 study testing Propranolol, Carvedilol and Rosuvastatin in people with Cirrhosis and Portal Hypertension, run by Universidade Federal do Rio de Janeiro at 1 site in Brazil.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cirrhosis, Portal Hypertension, Variceal Hemorrhage
- What is being tested?
- Propranolol, Carvedilol and Rosuvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteBrazil
- Study dates
- 25 Jan 2019to 20 Dec 2022
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Hepatic cirrhosis of any etiology
- Previous variceal bleeding
- Endoscopic variceal eradication at least 2 weeks before
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Brazil1 site, 1 recruiting
- Recruiting
Universidade Federal do Rio de Janeiro
Rio de Janeiro
Guilherme FM Rezende, MD, PhD, 55-21-999976292, guimottarezende@gmail.com
Andre Luiz M Torres, MD
About this study
Official title: Propranolol, Carvedilol and Rosuvastatin in the Prevention of Recurrent Variceal Haemorrhage in Patients With Cirrhotic Portal Hypertension
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.
- Conditions
- Cirrhosis, Portal Hypertension, Variceal Hemorrhage
- Being tested
- Propranolol, Carvedilol, Rosuvastatin, Placebo
- Medical subject headings
- Fibrosis, Hypertension, Portal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PropranololDrug
40mg to 320mg / day
CarvedilolDrug
6.25mg to 25mg / day
RosuvastatinDrug
20mg / day
PlaceboDrug
Placebo of rosuvastatin
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Propranolol |
| 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. Receives: Drug: Carvedilol |
| 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. Receives: Drug: Propranolol; Drug: Rosuvastatin |
| 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. Receives: Drug: Propranolol; Drug: Placebo |
| 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. Receives: Drug: Carvedilol; Drug: Rosuvastatin |
| 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. Receives: Drug: Carvedilol; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute hemodynamic response
A decrease in HVPG to 12 mmHg or lower
Measured: 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
Measured: 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
Measured: Eight weeks of beta blockers plus rosuvastatin or placebo
Secondary outcomes (2)
Sufficient hemodynamic response to beta blockers plus rosuvastatin or placebo
A decrease in HVPG of at least 20% from baseline
Measured: Eight weeks of beta blockers plus rosuvastatin or placebo
Partial hemodynamic response to beta blockers plus rosuvastatin or placebo
A decrease in HVPG of at least 10% from baseline
Measured: Eight weeks of beta blockers plus rosuvastatin or placebo
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2018
- Study start25 Jan 2019
- Primary completion20 Dec 2020 (estimated)
- Study completion20 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CirrhosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universidade Federal do Rio de Janeiro
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Guilherme Rezende, Universidade Federal do Rio de Janeiro
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03720067
- Sponsor's protocol ID
- 83211318.1.0000.5257
- Acronym
- Betastatin
- Status last verified
- May 2019
- First submitted
- 23 Oct 2018
- Last updated
- 14 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Propranolol, Carvedilol and Rosuvastatin in the Prevention of Recurrent Variceal Haemorrhage in Patients With Cirrhotic Portal Hypertension
- ClinicalTrials.gov ID
- NCT03720067
- Acronym / sponsor ID
- Betastatin / 83211318.1.0000.5257
- Conditions
- Cirrhosis, Portal Hypertension, Variceal Hemorrhage
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Universidade Federal do Rio de JaneiroUniversity, hospital or other
- Study start
- 25 Jan 2019 (actual)
- Primary completion
- 20 Dec 2020 (estimated)
- Study completion
- 20 Dec 2022 (estimated)
- First posted
- 25 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Phase 1: Propranolol (PPL) | Active comparator | Drug: PropranololHepatic 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 | Drug: CarvedilolHVPG 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 | Drug: Propranolol, Drug: RosuvastatinPatients 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 | Drug: Propranolol, Drug: PlaceboPatients 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 comparator | Drug: Carvedilol, Drug: RosuvastatinPatients 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 | Drug: Carvedilol, Drug: PlaceboPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Hepatic cirrhosis of any etiology
- Previous variceal bleeding
- Endoscopic variceal eradication at least 2 weeks before
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Propranolol40mg to 320mg / day | Drug | Phase 1: Propranolol (PPL), Phase 2: PPL non-responders/placebo, Phase 2: PPL non-responders/rosuvastatin |
| Carvedilol6.25mg to 25mg / day | Drug | Phase 1: Carvedilol (CVD), Phase 2: CVD non-responders/placebo, Phase 2: CVD non-responders/rosuvastatin |
| Rosuvastatin20mg / day | Drug | Phase 2: CVD non-responders/rosuvastatin, Phase 2: PPL non-responders/rosuvastatin |
| PlaceboPlacebo of rosuvastatin | Drug | Phase 2: CVD non-responders/placebo, Phase 2: PPL non-responders/placebo |
Primary outcome
Acute hemodynamic response
Time frame: 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
Time frame: 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
Time frame: Eight weeks of beta blockers plus rosuvastatin or placebo
A decrease in HVPG to 12 mmHg or lower
2 secondary outcomes
Sufficient hemodynamic response to beta blockers plus rosuvastatin or placebo
Time frame: Eight weeks of beta blockers plus rosuvastatin or placebo
Partial hemodynamic response to beta blockers plus rosuvastatin or placebo
Time frame: Eight weeks of beta blockers plus rosuvastatin or placebo
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Propranolol, Carvedilol and Rosuvastatin in people with Cirrhosis and Portal Hypertension, run by Universidade Federal do Rio de Janeiro at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Guilherme FM Rezende, MD, PhD ((5521)999976292, guimottarezende@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acute hemodynamic response (time frame: Two hours after a load dose of carvedilol or propranolol). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2019.