Liver Transplant; ComplicationsNCT03441035
Albumin Mass Balance in Liver Transplantation
An observational study of Liver Transplant; Complications and Fluid Overload, run by Ake Norberg at 1 site in Sweden.
Trial summary
This clinical observational cohort study assess the loss of albumin from blood circulation during and after liver transplantation by mass balance of albumin. The overall assumption of this method is that if albumin is more diluted than hemoglobin, it must have left the plasma, presumably into the interstitial space. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Liver Transplant; Complications, Fluid Overload
- What is being tested?
- General anesthesia and surgery (liver transplantation)
- Type of treatment
- Injection or infusion
- How many people
- 200 participants
- Where
- 1 siteSweden
- Study dates
- 27 Mar 2018to 30 Jun 2021
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: All patients undergoing liver transplantation at our unit (approximately 85 patients per year) will be asked to participate.
Who may be able to join
- All patients undergoing liver transplantation are eligible
Who cannot join
- No consent Unability to understand the study information (language or consciousness)
Trial locations and contacts
1 site in 1 country.
Sweden1 site, 1 recruiting
- Recruiting
Karolinska University Hospital, Huddinge
Huddinge, 14186
Åke Norberg, MD PhD, +46739661152, ake.norberg@sll.se
About this study
Official title: Albumin Mass Balance in Liver Transplantation, an Open Prospective Cohort Study
This clinical observational cohort study assess the loss of albumin from blood circulation during and after liver transplantation by mass balance of albumin. The overall assumption of this method is that if albumin is more diluted than hemoglobin, it must have left the plasma, presumably into the interstitial space. Predictors of albumin leakage will be assessed, including biomarkers of inflammation and of endothelial damage and dysfunction. The sub cohorts children and patients with complications, defined as prolonged postoperative treatment in the intensive care unit, respectively, will be focused in separate publications.
Read the detailed description
Background Capillary leakage has been recognized to be associated with surgery and inflammation [Fleck 1985]. In liver transplantation considerable amounts of exogenous albumin is administered to support circulatory stability and a post operative plasma albumin concentration of 25 g/L to facilitate interpretation of immuno suppressive drug concentrations. However, the long term effects of exogenous albumin is not well characterized in the literature, and extravasation might promote edema formation and impair wound healing. In previous studies we have demonstrated the ability of the albumin mass balance method to identify leakage of albumin in major abdominal surgery [Norberg 2016].
In a pilot study in patients undergoing liver transplantation (n=11) we found a net leakage of albumin from plasma of 37 ± 17 g at end of surgery and 48 ± 33 g at postoperative day 3.
The primary aim of the new study is to find if this net leakage is still there at postoperative day 7. We are also looking into predictors of positive albumin shift from plasma including markers of inflammation and endothelial injury or dysfunction. Focus will also be put on the subgroup of children during and after liver transplantation. Finally a subgroup of patients in need of prolonged ICU stay after liver transplantation will be investigated to see the prolonged effects of our present routines, and these patients ability to synthetize albumin.
All patients undergoing liver transplantation at Karolinska University Hospital are eligible.
Recruitment will be made in advance as soon as patients are put on the transplant waiting list. In adults, at the day of surgery, blood samples will be taken repeatedly for estimation of plasma albumin. In all patients we will keep track of any gains or losses of albumin or hemoglobin in suction bottles, drains, exogenous blood products, exogenous albumin etc. This sampling will proceed during the study period that will end at hospital discharge or not later than post-operative day 21. Adult patients that are still in the ICU on postoperative day 3 will be subjected to a measurement of albumin synthesis rate by the flooding method [Ballmer 1993]. All subjects, even children, will have blood sampled for ELISAs of markers of inflammation and endothelial injury or dysfunction.
Total study specific blood sampling will be limited to 100 mL in adults and 6 mL in children.
- Conditions
- Liver Transplant; Complications, Fluid Overload
- Being tested
- General anesthesia and surgery (liver transplantation)
- Medical subject headings
- Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
General anesthesia and surgery (liver transplantation)Other
The effects of general anesthesia and surgery under the hospital routine of albumin administration during and after liver transplantation is studied with the mass balance of albumin method.
| Study group | Role | What they receive |
|---|---|---|
| Adults, uncomplicated | Adults undergoing liver transplantation. Mass balance of albumin will be undertaken by sampling of albumin in plasma and in all fluids that is infused or lost from the body to keep track of albumin and hemoglobin changes until postoperative day 7. B-Hb is taken routinely and not study specific samples. Plasma for ELISAs is taken at 2-3 time points. Receives: Other: General anesthesia and surgery (liver transplantation) | |
| Adults, complicated | Adults undergoing liver transplantation. Mass balance of albumin will be undertaken by sampling of albumin in plasma and in all fluids that is infused or lost from the body to keep track of albumin and hemoglobin changes until hospital discharge or postoperative day 21. B-Hb is taken routinely and not study specific samples. Plasma for ELISAs is taken at 2-3 time points. A infusion of deuterium labeled phenylalanine will be given in the ICU at 1-3 occasions to determine the synthesis rate of albumin. Receives: Other: General anesthesia and surgery (liver transplantation) | |
| Children | Children undergoing liver transplantation. Mass balance of albumin will be undertaken by sampling of albumin in in all fluids that is infused or lost from the body to keep track of albumin and hemoglobin changes until postoperative day 7. P-albumin and B-Hb is only taken routinely and not study specific samples. Plasma for ELISAs is taken at 2-3 time points. Receives: Other: General anesthesia and surgery (liver transplantation) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative perioperative shift of albumin
By mass balance of albumin (i.e keeping track of all gains and losses of albumin and compare these to hemoglobin) it is possible to estimate the loss of albumin from plasma that is not explained by losses in bleeding or drains.
Measured: Post-operative day 7 after liver transplantation
Secondary outcomes (4)
Predictors of cumulative perioperative shift of albumin
anthropometric and laboratory values including markers of inflammation and endothelial injury or dysfunction will be analyzed by regression analysis to cumulative perioperative shift of albumin
Measured: from pre-operative risk assessment until post-operative day 7
Predictors of prolonged need for ICU stay
anthropometric and laboratory values including markers of inflammation and endothelial injury or dysfunction will be analyzed by regression analysis to Patients in need or not in need of prolonged ICU treatment
Measured: from pre-operative risk assessment until post-operative day 21
Albumin synthesis rate
By deuterium labeled phenylalanine it is possible to assess albumin synthesis rate by the "flooding technique"
Measured: postoperative days 3-21 after liver transplantation
Cumulative perioperative shift of albumin in children
By mass balance of albumin (i.e keeping track of all gains and losses of albumin and compare these to hemoglobin) it is possible to estimate the loss of albumin from plasma that is not explained by losses in bleeding or drains.
Measured: during and after liver transplantation until postoperative day 21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2018
- Study start27 Mar 2018
- Primary completion28 Feb 2021 (estimated)
- Study completion30 Jun 2021 (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 Liver Transplant; ComplicationsStudies 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
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ake Norberg
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Ake Norberg, Karolinska Institutet
- Investigators
- Åke Norberg, Ass Prof, Principal investigator, Perioperative Medicine and Intensive Care, Karolinska University Hospital Huddinge
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03441035
- Sponsor's protocol ID
- K2017-4774
- Other IDs
- 4-3344/2017
- Status last verified
- Sep 2020
- First submitted
- 15 Feb 2018
- Last updated
- 3 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fleck A, Raines G, Hawker F, Trotter J, Wallace PI, Ledingham IM, Calman KC. Increased vascular permeability: a major cause of hypoalbuminaemia in disease and injury. Lancet. 1985 Apr 6;1(8432):781-4. doi: 10.1016/s0140-6736(85)91447-3.
PubMed 2858667Norberg A, Rooyackers O, Segersvard R, Wernerman J. Leakage of albumin in major abdominal surgery. Crit Care. 2016 Apr 26;20(1):113. doi: 10.1186/s13054-016-1283-8.
PubMed 27117323Ballmer PE, McNurlan MA, Milne E, Heys SD, Buchan V, Calder AG, Garlick PJ. Measurement of albumin synthesis in humans: a new approach employing stable isotopes. Am J Physiol. 1990 Dec;259(6 Pt 1):E797-803. doi: 10.1152/ajpendo.1990.259.6.E797.
PubMed 2260648
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Albumin Mass Balance in Liver Transplantation, an Open Prospective Cohort Study
- ClinicalTrials.gov ID
- NCT03441035
- Acronym / sponsor ID
- K2017-4774
- Conditions
- Liver Transplant; Complications, Fluid Overload
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Ake NorbergUniversity, hospital or other
- Study start
- 27 Mar 2018 (actual)
- Primary completion
- 28 Feb 2021 (estimated)
- Study completion
- 30 Jun 2021 (estimated)
- First posted
- 22 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.
This clinical observational cohort study assess the loss of albumin from blood circulation during and after liver transplantation by mass balance of albumin. The overall assumption of this method is that if albumin is more diluted than hemoglobin, it must have left the plasma, presumably into the interstitial space. Predictors of albumin leakage will be assessed, including biomarkers of inflammation and of endothelial damage and dysfunction. The sub cohorts children and patients with complications, defined as prolonged postoperative treatment in the intensive care unit, respectively, will be focused in separate publications.
Detailed description
Background Capillary leakage has been recognized to be associated with surgery and inflammation [Fleck 1985]. In liver transplantation considerable amounts of exogenous albumin is administered to support circulatory stability and a post operative plasma albumin concentration of 25 g/L to facilitate interpretation of immuno suppressive drug concentrations. However, the long term effects of exogenous albumin is not well characterized in the literature, and extravasation might promote edema formation and impair wound healing. In previous studies we have demonstrated the ability of the albumin mass balance method to identify leakage of albumin in major abdominal surgery [Norberg 2016].
In a pilot study in patients undergoing liver transplantation (n=11) we found a net leakage of albumin from plasma of 37 ± 17 g at end of surgery and 48 ± 33 g at postoperative day 3.
The primary aim of the new study is to find if this net leakage is still there at postoperative day 7. We are also looking into predictors of positive albumin shift from plasma including markers of inflammation and endothelial injury or dysfunction. Focus will also be put on the subgroup of children during and after liver transplantation. Finally a subgroup of patients in need of prolonged ICU stay after liver transplantation will be investigated to see the prolonged effects of our present routines, and these patients ability to synthetize albumin.
All patients undergoing liver transplantation at Karolinska University Hospital are eligible.
Recruitment will be made in advance as soon as patients are put on the transplant waiting list. In adults, at the day of surgery, blood samples will be taken repeatedly for estimation of plasma albumin. In all patients we will keep track of any gains or losses of albumin or hemoglobin in suction bottles, drains, exogenous blood products, exogenous albumin etc. This sampling will proceed during the study period that will end at hospital discharge or not later than post-operative day 21. Adult patients that are still in the ICU on postoperative day 3 will be subjected to a measurement of albumin synthesis rate by the flooding method [Ballmer 1993]. All subjects, even children, will have blood sampled for ELISAs of markers of inflammation and endothelial injury or dysfunction.
Total study specific blood sampling will be limited to 100 mL in adults and 6 mL in children.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Adults, uncomplicated | – | Other: General anesthesia and surgery (liver transplantation)Adults undergoing liver transplantation. Mass balance of albumin will be undertaken by sampling of albumin in plasma and in all fluids that is infused or lost from the body to keep track of albumin and hemoglobin changes until postoperative day 7. B-Hb is taken routinely and not study specific samples. Plasma for ELISAs is taken at 2-3 time points. |
| Adults, complicated | – | Other: General anesthesia and surgery (liver transplantation)Adults undergoing liver transplantation. Mass balance of albumin will be undertaken by sampling of albumin in plasma and in all fluids that is infused or lost from the body to keep track of albumin and hemoglobin changes until hospital discharge or postoperative day 21. B-Hb is taken routinely and not study specific samples. Plasma for ELISAs is taken at 2-3 time points. A infusion of deuterium labeled phenylalanine will be given in the ICU at 1-3 occasions to determine the synthesis rate of albumin. |
| Children | – | Other: General anesthesia and surgery (liver transplantation)Children undergoing liver transplantation. Mass balance of albumin will be undertaken by sampling of albumin in in all fluids that is infused or lost from the body to keep track of albumin and hemoglobin changes until postoperative day 7. P-albumin and B-Hb is only taken routinely and not study specific samples. Plasma for ELISAs is taken at 2-3 time points. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- All patients undergoing liver transplantation at our unit (approximately 85 patients per year) will be asked to participate.
Key inclusion criteria (1 listed)
- All patients undergoing liver transplantation are eligible
Key exclusion criteria (1 listed)
- No consent Unability to understand the study information (language or consciousness)
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 |
|---|---|---|
| General anesthesia and surgery (liver transplantation)The effects of general anesthesia and surgery under the hospital routine of albumin administration during and after liver transplantation is studied with the mass balance of albumin method. | Other | Adults, complicated, Adults, uncomplicated, Children |
Primary outcome
Cumulative perioperative shift of albumin
Time frame: Post-operative day 7 after liver transplantation
By mass balance of albumin (i.e keeping track of all gains and losses of albumin and compare these to hemoglobin) it is possible to estimate the loss of albumin from plasma that is not explained by losses in bleeding or drains.
4 secondary outcomes
Predictors of cumulative perioperative shift of albumin
Time frame: from pre-operative risk assessment until post-operative day 7
Predictors of prolonged need for ICU stay
Time frame: from pre-operative risk assessment until post-operative day 21
Albumin synthesis rate
Time frame: postoperative days 3-21 after liver transplantation
Cumulative perioperative shift of albumin in children
Time frame: during and after liver transplantation until postoperative day 21
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2020.
- Background: PubMed 2858667Fleck A, Raines G, Hawker F, Trotter J, Wallace PI, Ledingham IM, Calman KC. Increased vascular permeability: a major cause of hypoalbuminaemia in disease and injury. Lancet. 1985 Apr 6;1(8432):781-4. doi: 10.1016/s0140-6736(85)91447-3.
- Background: PubMed 27117323Norberg A, Rooyackers O, Segersvard R, Wernerman J. Leakage of albumin in major abdominal surgery. Crit Care. 2016 Apr 26;20(1):113. doi: 10.1186/s13054-016-1283-8.
- Background: PubMed 2260648Ballmer PE, McNurlan MA, Milne E, Heys SD, Buchan V, Calder AG, Garlick PJ. Measurement of albumin synthesis in humans: a new approach employing stable isotopes. Am J Physiol. 1990 Dec;259(6 Pt 1):E797-803. doi: 10.1152/ajpendo.1990.259.6.E797.
- 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.
Åke Norberg, Ass Prof principal investigator
Perioperative Medicine and Intensive Care, Karolinska University Hospital Huddinge
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 Liver Transplant; Complications and Fluid Overload, run by Ake Norberg at 1 site in Sweden.
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 1 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 3 Sep 2020. 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 Sweden. 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 Åke Norberg, Ass Prof (+46739661152, ake.norberg@sll.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cumulative perioperative shift of albumin (time frame: Post-operative day 7 after liver transplantation). 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 NCT03441035, 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 3 Sep 2020.