End Stage Liver DiseaseNCT03633812
Effect of Preoperative Beta Blocker Use Postoperative Renal Function in the Patients Undergoing Liver Transplantation
An observational study of End Stage Liver Disease and Acute Kidney Injury, run by Asan Medical Center at 2 sites in South Korea.
Trial summary
This is prospective cohort study of patients classified by the premedication history of beta-blocker. The investigators aim to evaluate the hemodynamic effect of beta blocker through Swan-Ganz catheter monitoring and arterial pressure waveform analysis during surgery. Read more about this study
- Who is it for?
- Ages 20 to 65 years
- Conditions the study is for
- End Stage Liver Disease, Acute Kidney Injury
- What is being tested?
- Observational study, Beta blocker medication history
- How many people
- 477 participants
- Where
- 2 sitesSouth Korea
- Study dates
- 28 Oct 2016to 31 Dec 2020
- How long will I take part?
- 1 Year
- 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 20 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: living donor liver transplant recipients at Asan Medical Center, Seoul, Korea, Republic of
Who may be able to join
- living donor liver transplantation recipients
Who cannot join
- previous history of acute kidney injury
- previous liver transplantation history
- Fulminant hepatic failure
- history of TIPS, transjugular intrahepatic porto-systemic shunt
Trial locations and contacts
2 sites in 1 country.
South Korea2 sites, 2 recruiting
- Recruiting
Asan Medical Center
Seoul, 05505
Hye Won Jeong, M.D., 82-10-2531-9131, jklm110303@gmail.com
- Recruiting
Asan medical center
Seoul
Hye won Jeong, M.D., 82-10-2531-9131, jklm110303@gmail.com
About this study
Official title: The Effect of Preoperative Beta Blocker Use on Intraoperative Hemodynamics and Postoperative Renal Function in End-stage Liver Disease Patients Undergoing Liver Transplantation
This is prospective cohort study of patients classified by the premedication history of beta-blocker. The investigators aim to evaluate the hemodynamic effect of beta blocker through Swan-Ganz catheter monitoring and arterial pressure waveform analysis during surgery. The investigators also plan to observe the long-term effects of beta blocker on acute renal failure, allograft failure and mortality.
Read the detailed description
Since beta blockers have been shown to reduce portal venous pressure in 1980, the nonselective beta blocker (NSBB) has been widely used for the last 25 years as the primary treatment for portal hypertension. NSBB, such as propranolol and nadolol, has been shown to reduce cardiac output through β1 -receptor block and to constrict visceral vessels via β2-receptor block, thereby lowering portal venous pressure in patients with chronic liver disease. NSBB contributed to reducing complications such as esophageal variceal bleeding, ascites, hepatic encephalopathy, and improving survival in patients with cirrhosis. In addition, the use of NSBB in patients with ascites has been demonstrated to reduce the digestion time of intestinal food and reduce bacterial migration into the abdominal cavity and bloodstream.
On the other hand, recent studies have shown that NSBB use in the patients with advanced cirrhosis (accompanied by refractory ascites, spontaneous peritonitis, severe alcoholic hepatitis) may increase circulatory failure, acute renal failure, and mortality. When the cardiac index was less than 1.5 L / min / m² or the mean blood pressure was less than 80 mmHg in advanced cirrhosis with ascites, 1-year survival rate was found to be about 30% lower than the control. The use of beta blockers is argued to be avoided in the cirrhotic patients with refractory ascites because the mortality rate of these patients is associated with the use of beta blockers. These studies have been questioned in terms of reliability of the setting of treatment and control groups and correction of disturbance variables.
The window hypothesis has received attention for the risk-benefit of NSBB. This means that the beta blocker may be beneficial or harmful to the cirrhotic patients depending on the stage of disease progression. In conclusion, the use of beta-blockers in patients with early cirrhosis without moderate to large varix has no effect on prevention of esophageal varices, but is associated with depression, tiredness, sexual dysfunction, decreased cardiac output, increased risk of heart failure, symptomatic bradycardia, increased airway resistance, and bronchospasm. As the cirrhosis progresses, many changes occur in the cardiovascular system. The sympathetic nervous system and resin-angiotensin-aldosterone axis are up-regulated to compensate for the lack of effective blood volume due to peripheral vascular relaxation and hypotension. It is believed that the use of beta-blockers at this time may improve survival by reducing esophageal bleeding and bacterial migration. If the liver cirrhosis progresses more, the use of beta-blockers may compromise cardiac output, blood pressure, perfusion to important organs, thereby increasing the incidence of hepatorenal syndrome and mortality. The use of beta-blockers seems to be beneficial between the point of moderate to large varix generation to the point of advanced cirrhosis with undesired hemodynamic effect (spontaneous ascites, hepatorenal syndrome, spontaneous bacterial peritonitis, sepsis). The research is still ongoing and controversial.
As mentioned earlier, the use of beta blockers in patients with liver disease has been actively studied for the last 10 years, but most studies have been done in patients waiting for liver transplantation. Research is minimal in patients who actually undergo liver transplantation. In addition, studies have shown that beta blockers increase survival in patients waiting for liver transplantation by lowering portal venous pressure through beta 1, 2 -receptor block. But the actual research of preoperative beta blocker on perioperative hemodynamics, postoperative complications, and mortality is still lacking.
This is prospective cohort study of patients classified by the premedication history of beta-blocker. The investigators aim to evaluate the hemodynamic effect of beta blocker through Swan-Ganz catheter monitoring and arterial pressure waveform analysis during surgery. The investigators also plan to observe the long-term effects of beta blocker on acute renal failure, allograft failure and mortality.
- Conditions
- End Stage Liver Disease, Acute Kidney Injury
- Being tested
- Observational study, Beta blocker medication history
- Keywords
- End Stage Liver Disease, Acute Kidney Injury, Beta blocker
- Medical subject headings
- End Stage Liver Disease, Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Observational study, Beta blocker medication historyOther
Observational study, Beta blocker medication history
| Study group | Role | What they receive |
|---|---|---|
| Beta blocker group | ESLD recipients who had beta blocker during more than 1 month before the liver transplantation Receives: Other: Observational study, Beta blocker medication history | |
| Non-Beta blocker group | ESLD recipients who had not taken beta blocker more than 3 month before the liver transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute kidney injury
Creatinine change
Measured: 1 week
Secondary outcomes (2)
Graft failure
Graft failure
Measured: 1 year
Mortality
Mortality
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2018
- Study start28 Oct 2016
- Primary completion31 Dec 2019 (estimated)
- Study completion31 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for End Stage Liver DiseaseStudies 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
- 477 participants (estimated)
- Target duration
- 1 Year
Sponsor and investigators
- Lead sponsor
- Asan Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jun-Gol Song, Asan Medical Center
- Investigators
- Jun Gol Song, PH.D., Principal investigator, Asan Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03633812
- Sponsor's protocol ID
- 2016-1159
- Status last verified
- Aug 2018
- First submitted
- 14 Aug 2018
- Last updated
- 22 Aug 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Krag A, Wiest R, Albillos A, Gluud LL. The window hypothesis: haemodynamic and non-haemodynamic effects of beta-blockers improve survival of patients with cirrhosis during a window in the disease. Gut. 2012 Jul;61(7):967-9. doi: 10.1136/gutjnl-2011-301348. Epub 2012 Jan 10. No abstract available.
PubMed 22234982Serste T, Melot C, Francoz C, Durand F, Rautou PE, Valla D, Moreau R, Lebrec D. Deleterious effects of beta-blockers on survival in patients with cirrhosis and refractory ascites. Hepatology. 2010 Sep;52(3):1017-22. doi: 10.1002/hep.23775.
PubMed 20583214Serste T, Francoz C, Durand F, Rautou PE, Melot C, Valla D, Moreau R, Lebrec D. Beta-blockers cause paracentesis-induced circulatory dysfunction in patients with cirrhosis and refractory ascites: a cross-over study. J Hepatol. 2011 Oct;55(4):794-9. doi: 10.1016/j.jhep.2011.01.034. Epub 2011 Feb 24.
PubMed 21354230
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Preoperative Beta Blocker Use on Intraoperative Hemodynamics and Postoperative Renal Function in End-stage Liver Disease Patients Undergoing Liver Transplantation
- ClinicalTrials.gov ID
- NCT03633812
- Acronym / sponsor ID
- 2016-1159
- Conditions
- End Stage Liver Disease, Acute Kidney Injury
- Keywords
- End Stage Liver Disease, Acute Kidney Injury, Beta blocker
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 477 participants (estimated)
- Lead sponsor
- Asan Medical CenterUniversity, hospital or other
- Study start
- 28 Oct 2016 (actual)
- Primary completion
- 31 Dec 2019 (estimated)
- Study completion
- 31 Dec 2020 (estimated)
- First posted
- 16 Aug 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.
This is prospective cohort study of patients classified by the premedication history of beta-blocker. The investigators aim to evaluate the hemodynamic effect of beta blocker through Swan-Ganz catheter monitoring and arterial pressure waveform analysis during surgery. The investigators also plan to observe the long-term effects of beta blocker on acute renal failure, allograft failure and mortality.
Detailed description
Since beta blockers have been shown to reduce portal venous pressure in 1980, the nonselective beta blocker (NSBB) has been widely used for the last 25 years as the primary treatment for portal hypertension. NSBB, such as propranolol and nadolol, has been shown to reduce cardiac output through β1 -receptor block and to constrict visceral vessels via β2-receptor block, thereby lowering portal venous pressure in patients with chronic liver disease. NSBB contributed to reducing complications such as esophageal variceal bleeding, ascites, hepatic encephalopathy, and improving survival in patients with cirrhosis. In addition, the use of NSBB in patients with ascites has been demonstrated to reduce the digestion time of intestinal food and reduce bacterial migration into the abdominal cavity and bloodstream.
On the other hand, recent studies have shown that NSBB use in the patients with advanced cirrhosis (accompanied by refractory ascites, spontaneous peritonitis, severe alcoholic hepatitis) may increase circulatory failure, acute renal failure, and mortality. When the cardiac index was less than 1.5 L / min / m² or the mean blood pressure was less than 80 mmHg in advanced cirrhosis with ascites, 1-year survival rate was found to be about 30% lower than the control. The use of beta blockers is argued to be avoided in the cirrhotic patients with refractory ascites because the mortality rate of these patients is associated with the use of beta blockers. These studies have been questioned in terms of reliability of the setting of treatment and control groups and correction of disturbance variables.
The window hypothesis has received attention for the risk-benefit of NSBB. This means that the beta blocker may be beneficial or harmful to the cirrhotic patients depending on the stage of disease progression. In conclusion, the use of beta-blockers in patients with early cirrhosis without moderate to large varix has no effect on prevention of esophageal varices, but is associated with depression, tiredness, sexual dysfunction, decreased cardiac output, increased risk of heart failure, symptomatic bradycardia, increased airway resistance, and bronchospasm. As the cirrhosis progresses, many changes occur in the cardiovascular system. The sympathetic nervous system and resin-angiotensin-aldosterone axis are up-regulated to compensate for the lack of effective blood volume due to peripheral vascular relaxation and hypotension. It is believed that the use of beta-blockers at this time may improve survival by reducing esophageal bleeding and bacterial migration. If the liver cirrhosis progresses more, the use of beta-blockers may compromise cardiac output, blood pressure, perfusion to important organs, thereby increasing the incidence of hepatorenal syndrome and mortality. The use of beta-blockers seems to be beneficial between the point of moderate to large varix generation to the point of advanced cirrhosis with undesired hemodynamic effect (spontaneous ascites, hepatorenal syndrome, spontaneous bacterial peritonitis, sepsis). The research is still ongoing and controversial.
As mentioned earlier, the use of beta blockers in patients with liver disease has been actively studied for the last 10 years, but most studies have been done in patients waiting for liver transplantation. Research is minimal in patients who actually undergo liver transplantation. In addition, studies have shown that beta blockers increase survival in patients waiting for liver transplantation by lowering portal venous pressure through beta 1, 2 -receptor block. But the actual research of preoperative beta blocker on perioperative hemodynamics, postoperative complications, and mortality is still lacking.
This is prospective cohort study of patients classified by the premedication history of beta-blocker. The investigators aim to evaluate the hemodynamic effect of beta blocker through Swan-Ganz catheter monitoring and arterial pressure waveform analysis during surgery. The investigators also plan to observe the long-term effects of beta blocker on acute renal failure, allograft failure and mortality.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 1 Year
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Beta blocker group | – | Other: Observational study, Beta blocker medication historyESLD recipients who had beta blocker during more than 1 month before the liver transplantation |
| Non-Beta blocker group | – | –ESLD recipients who had not taken beta blocker more than 3 month before the liver transplantation |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- living donor liver transplant recipients at Asan Medical Center, Seoul, Korea, Republic of
Key inclusion criteria (1 listed)
- living donor liver transplantation recipients
Key exclusion criteria (4 listed)
- previous history of acute kidney injury
- previous liver transplantation history
- Fulminant hepatic failure
- history of TIPS, transjugular intrahepatic porto-systemic shunt
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 |
|---|---|---|
| Observational study, Beta blocker medication historyObservational study, Beta blocker medication history | Other | Beta blocker group |
Primary outcome
Acute kidney injury
Time frame: 1 week
Creatinine change
2 secondary outcomes
Graft failure
Time frame: 1 year
Mortality
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2018.
- Background: PubMed 22234982Krag A, Wiest R, Albillos A, Gluud LL. The window hypothesis: haemodynamic and non-haemodynamic effects of beta-blockers improve survival of patients with cirrhosis during a window in the disease. Gut. 2012 Jul;61(7):967-9. doi: 10.1136/gutjnl-2011-301348. Epub 2012 Jan 10. No abstract available.
- Background: PubMed 20583214Serste T, Melot C, Francoz C, Durand F, Rautou PE, Valla D, Moreau R, Lebrec D. Deleterious effects of beta-blockers on survival in patients with cirrhosis and refractory ascites. Hepatology. 2010 Sep;52(3):1017-22. doi: 10.1002/hep.23775.
- Background: PubMed 21354230Serste T, Francoz C, Durand F, Rautou PE, Melot C, Valla D, Moreau R, Lebrec D. Beta-blockers cause paracentesis-induced circulatory dysfunction in patients with cirrhosis and refractory ascites: a cross-over study. J Hepatol. 2011 Oct;55(4):794-9. doi: 10.1016/j.jhep.2011.01.034. Epub 2011 Feb 24.
- 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.
Jun Gol Song, PH.D. principal investigator
Asan Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of End Stage Liver Disease and Acute Kidney Injury, run by Asan Medical Center at 2 sites in South Korea.
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 1 inclusion and 4 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 22 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in South Korea. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hye Won Jeong, M.D. (82-10-2531-9131, jklm110303@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acute kidney injury (time frame: 1 week). 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 NCT03633812, which also lists 3 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 22 Aug 2018.