Portal HypertensionNCT03438916
MRI to Assess the Effect of Non-selective Beta-blocker in Patients With Cirrhosis
An observational study of Portal Hypertension and Cirrhosis, run by Hvidovre University Hospital at 1 site in Denmark.
Trial summary
Background: Standardization and new therapeutic treatments of variceal bleeding has significantly reduced the mortality the last 25 years, but there is still a high 6-week mortality around 15-20% and 1-year mortality of about 40%. Read more about this study
- Who is it for?
- Ages 18 to 78 years
- Conditions the study is for
- Portal Hypertension, Cirrhosis, Esophageal Varices
- How many people
- 40 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Apr 2017to 8 Dec 2020
- Phase
- Observational
- 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 to 78 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 39 patients with cirrhosis and esophageal varices that require NSBB (propranolol) treatment.
Who may be able to join
- Patients with cirrhosis and esophageal varices that require NSBB treatment
- Patients of more than 18 and less than 78 years of age
- Patients with a portal pressure HVPG ≥ 12mmHg
Who cannot join
- Patients who are unable to give informed consent
- Patients with absolute contraindication for MRI
- Patients with absolute contraindication for NSBB
- Pregnant women
- Patient with severe hemodynamic comorbidity
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Centre of Gastroenterology, Dept. of medicine. Hvidovre University Hospital
Hvidovre, 2650
About this study
Official title: Hemodynamic Alterations in Liver Cirrhosis Validated by Non-invasive MRI Compared to Invasive Assessment: Can MRI and Echocardiography Predict the Pharmacological Response of Non-selective Beta-blocker in Patients With Cirrhosis?
Background:
Standardization and new therapeutic treatments of variceal bleeding has significantly reduced the mortality the last 25 years, but there is still a high 6-week mortality around 15-20% and 1-year mortality of about 40%. Cirrhotic patients without prophylactic treatment suffer a risk of 60% of re-bleeding within the first year after the first bleeding episode. Variceal ligation and NSBB are the standard therapy as secondary prophylaxis, while only non-selective beta-blocker (NSBB) is offered as first-line therapy in primary prophylaxis. If portal pressure is reduced to a value below 12 mmHg or by 20% (10% if assessed by intravenous administrations), the risk of bleeding is substantially reduced, but not all patients respond to the treatment with propranolol (40-50%). Hence, patients who are non-responders to NSBB should be offered alternative treatment with e.g. carvedilol, which is a combined alpha-beta-receptor blocker or endoscopic band ligation. Currently, the response to NSBB is assessed invasively during a liver vein catheterization (LVC). Unfortunately, only a few centres in the world can perform this procedure and there are no reliable non-invasive alternatives to assess the respond to NSBB, which is of extreme importance, since non-responders have three fold increased risk of a new variceal bleeding episode.
Read more
Aim:
In general the aim of the project is to develop faster and non-invasive methods to evaluate portal hypertension and individual pharmacological response of NSBB in patients with cirrhosis. Furthermore, we expect to detect changes in liver and spleen stiffness as measured by MR-Elastography (MRE) after NSBB and that these depend on the drug-related effects on portal pressure.
Study design and patients:
39 patients with cirrhosis and esophageal varices that require NSBB (propranolol) treatment.
Patients are assessed with LVC, MR-scans, echocardiography and biochemical tests. LVC is the gold standard method to test if patients respond to propranolol treatment. At visit 1. the response to NSBB is defined as a reduction of HVPG ≥10%, or to a HVPG< 12mmHg after intravenous NSBB administrations during LVC. MRI-scan with intraveneus NSBB administration is performed at visit 2. Minimum 5 days of NSBB wash out between visit 1 and 2.
Read the detailed description
MR-elastography and Phase Contrast MRI compared to LVC
- Conditions
- Portal Hypertension, Cirrhosis, Esophageal Varices, Gastric Varices Bleeding, Varice Bleed, Liver Diseases
- Keywords
- Non-selective beta-blocker, Pharmacological respons, Magnetic Resonance Imaging, Hemodynamic assessments, Echocardiography, MR-elastography, Propranolol, Liver vein catheterization
- Medical subject headings
- Hypertension, Portal, Fibrosis, Esophageal and Gastric Varices, Liver Diseases, Liver Cirrhosis
What is being measured
The primary outcome is the main question the study is designed to answer.
NSBB response defined as a reduction in HVPG >10% or HVPG <12 mmHG after intraveneus NSBB administrations compared to flow (mL/min) in splanchnic vessels
To assess if changes in MR flow induced with NSBB (propranolol) administrations can predict the changes in HVPG after NSBB administration (NSBB respons) assessed by LVC
Measured: after 20 minutes respons time
Secondary outcomes (1)
MR-elastography
To assess the liver and spleen stiffness (kPa) with MRE before and after intraveneus NSBB administration
Measured: after 20 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2018
- Study start1 Apr 2017
- Primary completion8 Dec 2020
- Study completion8 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Portal HypertensionStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hvidovre University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Flemming Bendtsen, Hvidovre University Hospital
- Investigators
- Flemming Bendtsen, Professor, Principal investigator, Professor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03438916
- Sponsor's protocol ID
- 16048475
- Status last verified
- Mar 2023
- First submitted
- 10 Feb 2018
- Last updated
- 14 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Danielsen KV, Nabilou P, Wiese SS, Hove JD, Bendtsen F, Moller S. Effect of beta-blockers on multiple haemodynamics in cirrhosis: A cross-over study by MR-imaging and hepatic vein catheterization. Liver Int. 2023 Oct;43(10):2245-2255. doi: 10.1111/liv.15664. Epub 2023 Jun 30.
PubMed 37387503Danielsen KV, Hove JD, Nabilou P, Yin M, Chen J, Zhao M, Kallemose T, Teisner AS, Siebner HR, Ehman RL, Moller S, Bendtsen F. Using MR elastography to assess portal hypertension and response to beta-blockers in patients with cirrhosis. Liver Int. 2021 Sep;41(9):2149-2158. doi: 10.1111/liv.14981. Epub 2021 Jun 16.
PubMed 34060714
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hemodynamic Alterations in Liver Cirrhosis Validated by Non-invasive MRI Compared to Invasive Assessment: Can MRI and Echocardiography Predict the Pharmacological Response of Non-selective Beta-blocker in Patients With Cirrhosis?
- ClinicalTrials.gov ID
- NCT03438916
- Acronym / sponsor ID
- 16048475
- Conditions
- Portal Hypertension, Cirrhosis, Esophageal Varices, Gastric Varices Bleeding, Varice Bleed, Liver Diseases
- Keywords
- Non-selective beta-blocker, Pharmacological respons, Magnetic Resonance Imaging, Hemodynamic assessments, Echocardiography, MR-elastography, Propranolol, Liver vein catheterization
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Hvidovre University HospitalUniversity, hospital or other
- Study start
- 1 Apr 2017 (actual)
- Primary completion
- 8 Dec 2020 (actual)
- Study completion
- 8 Dec 2020 (actual)
- First posted
- 20 Feb 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.
Background:
Standardization and new therapeutic treatments of variceal bleeding has significantly reduced the mortality the last 25 years, but there is still a high 6-week mortality around 15-20% and 1-year mortality of about 40%. Cirrhotic patients without prophylactic treatment suffer a risk of 60% of re-bleeding within the first year after the first bleeding episode. Variceal ligation and NSBB are the standard therapy as secondary prophylaxis, while only non-selective beta-blocker (NSBB) is offered as first-line therapy in primary prophylaxis. If portal pressure is reduced to a value below 12 mmHg or by 20% (10% if assessed by intravenous administrations), the risk of bleeding is substantially reduced, but not all patients respond to the treatment with propranolol (40-50%). Hence, patients who are non-responders to NSBB should be offered alternative treatment with e.g. carvedilol, which is a combined alpha-beta-receptor blocker or endoscopic band ligation. Currently, the response to NSBB is assessed invasively during a liver vein catheterization (LVC). Unfortunately, only a few centres in the world can perform this procedure and there are no reliable non-invasive alternatives to assess the respond to NSBB, which is of extreme importance, since non-responders have three fold increased risk of a new variceal bleeding episode.
Aim:
In general the aim of the project is to develop faster and non-invasive methods to evaluate portal hypertension and individual pharmacological response of NSBB in patients with cirrhosis. Furthermore, we expect to detect changes in liver and spleen stiffness as measured by MR-Elastography (MRE) after NSBB and that these depend on the drug-related effects on portal pressure.
Study design and patients:
39 patients with cirrhosis and esophageal varices that require NSBB (propranolol) treatment.
Patients are assessed with LVC, MR-scans, echocardiography and biochemical tests. LVC is the gold standard method to test if patients respond to propranolol treatment. At visit 1. the response to NSBB is defined as a reduction of HVPG ≥10%, or to a HVPG< 12mmHg after intravenous NSBB administrations during LVC. MRI-scan with intraveneus NSBB administration is performed at visit 2. Minimum 5 days of NSBB wash out between visit 1 and 2.
Detailed description
MR-elastography and Phase Contrast MRI compared to LVC
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 78 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 39 patients with cirrhosis and esophageal varices that require NSBB (propranolol) treatment.
Key inclusion criteria (3 listed)
- Patients with cirrhosis and esophageal varices that require NSBB treatment
- Patients of more than 18 and less than 78 years of age
- Patients with a portal pressure HVPG ≥ 12mmHg
Key exclusion criteria (5 listed)
- Patients who are unable to give informed consent
- Patients with absolute contraindication for MRI
- Patients with absolute contraindication for NSBB
- Pregnant women
- Patient with severe hemodynamic comorbidity
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
NSBB response defined as a reduction in HVPG >10% or HVPG <12 mmHG after intraveneus NSBB administrations compared to flow (mL/min) in splanchnic vessels
Time frame: after 20 minutes respons time
To assess if changes in MR flow induced with NSBB (propranolol) administrations can predict the changes in HVPG after NSBB administration (NSBB respons) assessed by LVC
1 secondary outcome
MR-elastography
Time frame: after 20 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2023.
- Derived from this study: PubMed 37387503Danielsen KV, Nabilou P, Wiese SS, Hove JD, Bendtsen F, Moller S. Effect of beta-blockers on multiple haemodynamics in cirrhosis: A cross-over study by MR-imaging and hepatic vein catheterization. Liver Int. 2023 Oct;43(10):2245-2255. doi: 10.1111/liv.15664. Epub 2023 Jun 30.
- Derived from this study: PubMed 34060714Danielsen KV, Hove JD, Nabilou P, Yin M, Chen J, Zhao M, Kallemose T, Teisner AS, Siebner HR, Ehman RL, Moller S, Bendtsen F. Using MR elastography to assess portal hypertension and response to beta-blockers in patients with cirrhosis. Liver Int. 2021 Sep;41(9):2149-2158. doi: 10.1111/liv.14981. Epub 2021 Jun 16.
- Individual participant dataSharing planned: Undecided
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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.
Flemming Bendtsen, Professor principal investigator
Professor
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Portal Hypertension and Cirrhosis, run by Hvidovre University Hospital at 1 site in Denmark.
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 5 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: finished, as of the sponsor's last update on 14 Mar 2023. 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 Denmark. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
NSBB response defined as a reduction in HVPG >10% or HVPG <12 mmHG after intraveneus NSBB administrations compared to flow (mL/min) in splanchnic vessels (time frame: after 20 minutes respons time). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03438916, which also lists 2 linked publications.
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 Mar 2023.