AscitesNCT02811406
The Role of Intravenous Albumin Replacement During Abdominal Paracentesis in Patients With Malignancy Related Ascites
A study testing Receives IV albumin infusion and Do not receive IV albumin infusion in people with Ascites and Hypotension, run by National University Hospital, Singapore at 1 site in Singapore.
Trial summary
Aims: To compare the rates of hypotension in patients with malignancy-related ascites undergoing abdominal paracentesis with and without prophylactic intravenous albumin infusion Methodology: Patients with symptomatic ascites secondary to underlying malignancy admitted to medical oncology inpatient service who require… Read more about this study
- Who is it for?
- Ages 21 to 99 years
- Conditions the study is for
- Ascites, Hypotension
- What is being tested?
- Receives IV albumin infusion and Do not receive IV albumin infusion
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteSingapore
- Study dates
- Jun 2016to Dec 2017
- Phase
- Interventional
- 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 21 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age more than 21 years old
- Inpatients admitted to medical oncology service with symptomatic ascites and who are scheduled for abdominal paracentesis
- Known underlying malignancy
- Blood pressure before abdominal paracentesis more than 90/50 mmHg
Who cannot join
- Patients with known portal hypertension, defined by serum albumin: ascites gradient (SAAG) more than 11.1 mmol/L, based on previous results in last 1 year
- Patients with a known history of hypotension when getting paracentesis
- Pregnant women
Trial locations and contacts
1 site in 1 country.
Singapore1 site, 1 recruiting
- Recruiting
National University Hospital
Singapore, Singapore, 164119
Soo Chin Lee, (65) 6779 5555, soo_chin_lee@nuhs.edu.sg
Gloria Hui Jia Chan, (65) 6779 5555, gloria_chan@nuhs.edu.sg
About this study
Aims: To compare the rates of hypotension in patients with malignancy-related ascites undergoing abdominal paracentesis with and without prophylactic intravenous albumin infusion
Methodology: Patients with symptomatic ascites secondary to underlying malignancy admitted to medical oncology inpatient service who require abdominal paracentesis will be enrolled. Patients with known portal hypertension based on SAAG (>11.1 mmol/L) will be excluded. Eligible patients are randomized 1:1 to two groups. During drainage of ascites fluid, one group will receive intravenous albumin infusion (50 ml/Litre of ascitic fluid drained), whereas the other group will not receive intravenous albumin infusion. Baseline parameters along with routine 4 hourly monitoring of blood pressure will be done. Episodes of hypotension (fall in SBP > 20 mmHg) will be compared between these two groups and significance tested using the chi-square test.
Clinical significance: Ascites often occurs in the setting of advanced malignancy and drainage of ascites has been proven to provide symptomatic relief in this patient population with relatively short life expectancy. The use of intravenous albumin infusion is loosely extrapolated from studies in patients with liver cirrhosis undergoing abdominal paracentesis. To date, there have been no standard guidelines to guide practice and no studies looking at the use of intravenous albumin in this population. As the mechanisms of ascites are different in different malignancies, the indication of intravenous albumin is uncertain and perhaps unnecessary in this setting. We hope to understand more about the rates of hypotension during abdominal paracentesis in this population and to generate systematic data to guide clinical practice in this area.
Read the detailed description
General Introduction:
Therapeutic paracentesis is the first line of treatment for patients with symptomatic malignant ascites. The practice of intravenous albumin infusion during abdominal paracentesis comes from evidence in patients with liver cirrhosis. A meta-analysis of seventeen randomised trials evaluating patients receiving albumin versus alternative treatment during large volume paracentesis found that albumin reduced the incidence of post-paracentesis circulatory dysfunction, hyponatraemia and mortality (Bernardi M, 2012). The mechanisms of ascites in patients with cirrhosis are driven by portal hypertension. Portal hypertension brings about systemic vasodilation and hyperdynamic circulation that eventually contribute to functional and biochemical changes leading to ascites (Gines. P, 1997).
In contrast, cause of ascites in patients with malignancies is usually multi-factorial. It occurs commonly in several tumours including malignancies of ovary, breast, colon, lung, pancreas and liver. In each of these cancer types, the mechanisms leading to malignancy-related ascites may be different. Peritoneal carcinomatosis is a major cause of malignancy-related ascites. Other causes include massive liver metastasis causing portal hypertension, chronic hypoalbuminaemia, hepatocellular carcinoma, chylous ascites from lymphoma and Budd-Chiari syndrome due to occlusion of hepatic veins (Runyon BA, 1988).
In patients with cancer, aside from those who develop ascites as a result of portal hypertension, the benefit of intravenous albumin infusion with large volume paracentesis is uncertain, if at all present. Locally, the current clinical practice is for infusion of intravenous albumin during abdominal paracentesis in patients with malignancy-related ascites regardless of cause. The drawbacks of such an approach include exposing patients to risk of anaphylaxis and increased financial costs (50 ml of 20% Albumin costs $42).
Granted that the potential harms of albumin infusion are rare, the burden of proof to show that an intervention works is held by those who introduce it. To date, there have been no studies specifically examining the role of intravenous albumin infusion in this population. In the setting of advanced cancer where life expectancy is limited, the most clinically relevant benefit of albumin infusion would be to reduce the rates of post-paracentesis circulatory dysfunction. Through a pilot study, we hope to evaluate the effectiveness of IV albumin in reducing rates of hypotension, thereby guiding clinical practice in this area.
Rationale and justification for the Study:
Hypothesis: Intravenous albumin infusion during abdominal paracentesis does not prevent hypotension in patients with malignancy-related ascites without portal hypertension.
Rationale for the Study Purpose:
Three significant outcomes have been proven for the use of intravenous albumin in large volume paracentesis in patients with cirrhosis. These are prevention of hypotension, prevention of hyponatraemia and survival benefit. Ascites in the setting of patients with malignancy usually occurs in advanced stage, of which the most meaningful outcome would be that of prevention of hypotension. At present, the current clinical practice locally is extrapolated from studies in patients with cirrhosis, and some physicians would opt to administer IV albumin with every litre of ascitic fluid drained. We propose a study to compare the rates of hypotension in patients who received IV albumin and those who do not. In this study, we will randomise patients with a known history of cancer who are admitted for symptomatic ascites to two groups. Both groups of patients will undergo insertion of abdominal drain for symptomatic relief. Group 1 will receive intravenous albumin and Group 2 will not.
Rationale for Doses Selected:
In Group 1, 50 ml of 20% intravenous albumin will be given for every litre of ascitic fluid drained as this is the current local preparation and practice.
Rationale for Study Population:
Replacement of intravenous albumin has been established in patients with ascites drainage for patients with liver cirrhosis. It has not been shown to benefit patients with malignancy.
Rationale for Study Design:
There have been no previous studies in patients of this population. This is a prospective pilot randomised study in order to compare the rates of hypotension between the two groups.
- Conditions
- Ascites, Hypotension
- Being tested
- Receives IV albumin infusion, Do not receive IV albumin infusion
- Medical subject headings
- Ascites, Hypotension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Receives IV albumin infusionProcedure or surgery
IV albumin 20% 50 mL for every 1L of ascitic fluid drained. Blood pressure and heart rate are recorded every four hours in both groups in the first 48 hours.
If hypotension occurs (defined as fall in systolic blood pressure of > 20 mmHg from baseline) during drainage, drain is clamped and the patient will be clinically evaluated for cause of hypotension. If no other causes of hypotension are found and patient remains asymptomatic, repeat blood pressure measurement in 30 minutes. If blood pressure maintains > 90/50 mmHg after 30 minutes and patient is asymptomatic, continue drainage and patient stays in the study. If patient remains hypotensive (BP < 90/50) or develops symptomatic hypotension, then the patient will be taken off study and the hypotension managed as clinically indicated.
Do not receive IV albumin infusionBiological
No IV albumin infusion. Blood pressure and heart rate are recorded every four hours in both groups in the first 48 hours.
If hypotension occurs (defined as fall in systolic blood pressure of > 20 mmHg from baseline) during drainage, drain is clamped and the patient will be clinically evaluated for cause of hypotension. If no other causes of hypotension are found and patient remains asymptomatic, repeat blood pressure measurement in 30 minutes. If blood pressure maintains > 90/50 mmHg after 30 minutes and patient is asymptomatic, continue drainage and patient stays in the study. If patient remains hypotensive (BP < 90/50) or develops symptomatic hypotension, then the patient will be taken off study and the hypotension managed as clinically indicated.
| Study group | Role | What they receive |
|---|---|---|
| Receives IV albumin infusion | Experimental | IV albumin 20% 50 mL for every 1L of ascitic fluid drained Receives: Procedure: Receives IV albumin infusion |
| Do not receive IV albumin infusion | Placebo comparator | No IV albumin infusion Receives: Biological: Do not receive IV albumin infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rates of hypotension
Measured: For 48 hours since start of drainage
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2016 (estimated)
- Study startJun 2016
- Primary completionJun 2017 (estimated)
- Study completionDec 2017 (estimated)
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 AscitesStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Soo Chin Lee, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02811406
- Sponsor's protocol ID
- MC01/02/16
- Other IDs
- 2016/00326, 2016
- Status last verified
- Jun 2016
- First submitted
- 21 Jun 2016
- Last updated
- 23 Jun 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Bernardi M, Caraceni P, Navickis RJ, Wilkes MM. Albumin infusion in patients undergoing large-volume paracentesis: a meta-analysis of randomized trials. Hepatology. 2012 Apr;55(4):1172-81. doi: 10.1002/hep.24786.
PubMed 22095893Grabau CM, Crago SF, Hoff LK, Simon JA, Melton CA, Ott BJ, Kamath PS. Performance standards for therapeutic abdominal paracentesis. Hepatology. 2004 Aug;40(2):484-8. doi: 10.1002/hep.20317.
PubMed 15368454
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Intravenous Albumin Replacement During Abdominal Paracentesis in Patients With Malignancy Related Ascites
- ClinicalTrials.gov ID
- NCT02811406
- Acronym / sponsor ID
- MC01/02/16
- Conditions
- Ascites, Hypotension
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Study start
- Jun 2016
- Primary completion
- Jun 2017 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 23 Jun 2016 (estimated)
- 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.
Aims: To compare the rates of hypotension in patients with malignancy-related ascites undergoing abdominal paracentesis with and without prophylactic intravenous albumin infusion
Methodology: Patients with symptomatic ascites secondary to underlying malignancy admitted to medical oncology inpatient service who require abdominal paracentesis will be enrolled. Patients with known portal hypertension based on SAAG (>11.1 mmol/L) will be excluded. Eligible patients are randomized 1:1 to two groups. During drainage of ascites fluid, one group will receive intravenous albumin infusion (50 ml/Litre of ascitic fluid drained), whereas the other group will not receive intravenous albumin infusion. Baseline parameters along with routine 4 hourly monitoring of blood pressure will be done. Episodes of hypotension (fall in SBP > 20 mmHg) will be compared between these two groups and significance tested using the chi-square test.
Clinical significance: Ascites often occurs in the setting of advanced malignancy and drainage of ascites has been proven to provide symptomatic relief in this patient population with relatively short life expectancy. The use of intravenous albumin infusion is loosely extrapolated from studies in patients with liver cirrhosis undergoing abdominal paracentesis. To date, there have been no standard guidelines to guide practice and no studies looking at the use of intravenous albumin in this population. As the mechanisms of ascites are different in different malignancies, the indication of intravenous albumin is uncertain and perhaps unnecessary in this setting. We hope to understand more about the rates of hypotension during abdominal paracentesis in this population and to generate systematic data to guide clinical practice in this area.
Detailed description
General Introduction:
Therapeutic paracentesis is the first line of treatment for patients with symptomatic malignant ascites. The practice of intravenous albumin infusion during abdominal paracentesis comes from evidence in patients with liver cirrhosis. A meta-analysis of seventeen randomised trials evaluating patients receiving albumin versus alternative treatment during large volume paracentesis found that albumin reduced the incidence of post-paracentesis circulatory dysfunction, hyponatraemia and mortality (Bernardi M, 2012). The mechanisms of ascites in patients with cirrhosis are driven by portal hypertension. Portal hypertension brings about systemic vasodilation and hyperdynamic circulation that eventually contribute to functional and biochemical changes leading to ascites (Gines. P, 1997).
In contrast, cause of ascites in patients with malignancies is usually multi-factorial. It occurs commonly in several tumours including malignancies of ovary, breast, colon, lung, pancreas and liver. In each of these cancer types, the mechanisms leading to malignancy-related ascites may be different. Peritoneal carcinomatosis is a major cause of malignancy-related ascites. Other causes include massive liver metastasis causing portal hypertension, chronic hypoalbuminaemia, hepatocellular carcinoma, chylous ascites from lymphoma and Budd-Chiari syndrome due to occlusion of hepatic veins (Runyon BA, 1988).
In patients with cancer, aside from those who develop ascites as a result of portal hypertension, the benefit of intravenous albumin infusion with large volume paracentesis is uncertain, if at all present. Locally, the current clinical practice is for infusion of intravenous albumin during abdominal paracentesis in patients with malignancy-related ascites regardless of cause. The drawbacks of such an approach include exposing patients to risk of anaphylaxis and increased financial costs (50 ml of 20% Albumin costs $42).
Granted that the potential harms of albumin infusion are rare, the burden of proof to show that an intervention works is held by those who introduce it. To date, there have been no studies specifically examining the role of intravenous albumin infusion in this population. In the setting of advanced cancer where life expectancy is limited, the most clinically relevant benefit of albumin infusion would be to reduce the rates of post-paracentesis circulatory dysfunction. Through a pilot study, we hope to evaluate the effectiveness of IV albumin in reducing rates of hypotension, thereby guiding clinical practice in this area.
Rationale and justification for the Study:
Hypothesis: Intravenous albumin infusion during abdominal paracentesis does not prevent hypotension in patients with malignancy-related ascites without portal hypertension.
Rationale for the Study Purpose:
Three significant outcomes have been proven for the use of intravenous albumin in large volume paracentesis in patients with cirrhosis. These are prevention of hypotension, prevention of hyponatraemia and survival benefit. Ascites in the setting of patients with malignancy usually occurs in advanced stage, of which the most meaningful outcome would be that of prevention of hypotension. At present, the current clinical practice locally is extrapolated from studies in patients with cirrhosis, and some physicians would opt to administer IV albumin with every litre of ascitic fluid drained. We propose a study to compare the rates of hypotension in patients who received IV albumin and those who do not. In this study, we will randomise patients with a known history of cancer who are admitted for symptomatic ascites to two groups. Both groups of patients will undergo insertion of abdominal drain for symptomatic relief. Group 1 will receive intravenous albumin and Group 2 will not.
Rationale for Doses Selected:
In Group 1, 50 ml of 20% intravenous albumin will be given for every litre of ascitic fluid drained as this is the current local preparation and practice.
Rationale for Study Population:
Replacement of intravenous albumin has been established in patients with ascites drainage for patients with liver cirrhosis. It has not been shown to benefit patients with malignancy.
Rationale for Study Design:
There have been no previous studies in patients of this population. This is a prospective pilot randomised study in order to compare the rates of hypotension between the two groups.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Receives IV albumin infusion | Experimental | Procedure: Receives IV albumin infusionIV albumin 20% 50 mL for every 1L of ascitic fluid drained |
| Do not receive IV albumin infusion | Placebo comparator | Biological: Do not receive IV albumin infusionNo IV albumin infusion |
Who may qualify
- Ages
- 21 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age more than 21 years old
- Inpatients admitted to medical oncology service with symptomatic ascites and who are scheduled for abdominal paracentesis
- Known underlying malignancy
- Blood pressure before abdominal paracentesis more than 90/50 mmHg
Key exclusion criteria (3 listed)
- Patients with known portal hypertension, defined by serum albumin: ascites gradient (SAAG) more than 11.1 mmol/L, based on previous results in last 1 year
- Patients with a known history of hypotension when getting paracentesis
- Pregnant women
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 |
|---|---|---|
| Receives IV albumin infusionIV albumin 20% 50 mL for every 1L of ascitic fluid drained. Blood pressure and heart rate are recorded every four hours in both groups in the first 48 hours. If hypotension occurs (defined as fall in systolic blood pressure of > 20 mmHg from baseline) during drainage, drain is clamped and the patient will be clinically evaluated for cause of hypotension. If no other causes of hypotension are found and patient remains asymptomatic, repeat blood pressure measurement in 30 minutes. If blood pressure maintains > 90/50 mmHg after 30 minutes and patient is asymptomatic, continue drainage and patient stays in the study. If patient remains hypotensive (BP < 90/50) or develops symptomatic hypotension, then the patient will be taken off study and the hypotension managed as clinically indicated. | Procedure or surgery | Receives IV albumin infusion |
| Do not receive IV albumin infusionNo IV albumin infusion. Blood pressure and heart rate are recorded every four hours in both groups in the first 48 hours. If hypotension occurs (defined as fall in systolic blood pressure of > 20 mmHg from baseline) during drainage, drain is clamped and the patient will be clinically evaluated for cause of hypotension. If no other causes of hypotension are found and patient remains asymptomatic, repeat blood pressure measurement in 30 minutes. If blood pressure maintains > 90/50 mmHg after 30 minutes and patient is asymptomatic, continue drainage and patient stays in the study. If patient remains hypotensive (BP < 90/50) or develops symptomatic hypotension, then the patient will be taken off study and the hypotension managed as clinically indicated. | Biological | Do not receive IV albumin infusion |
Primary outcome
Rates of hypotension
Time frame: For 48 hours since start of drainage
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2016.
- Background: PubMed 22095893Bernardi M, Caraceni P, Navickis RJ, Wilkes MM. Albumin infusion in patients undergoing large-volume paracentesis: a meta-analysis of randomized trials. Hepatology. 2012 Apr;55(4):1172-81. doi: 10.1002/hep.24786.
- Background: PubMed 15368454Grabau CM, Crago SF, Hoff LK, Simon JA, Melton CA, Ott BJ, Kamath PS. Performance standards for therapeutic abdominal paracentesis. Hepatology. 2004 Aug;40(2):484-8. doi: 10.1002/hep.20317.
- 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.
Soo Chin Lee principal investigator
National University Hospital, Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Receives IV albumin infusion and Do not receive IV albumin infusion in people with Ascites and Hypotension, run by National University Hospital, Singapore at 1 site in Singapore.
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 4 inclusion and 3 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 23 Jun 2016. 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 Singapore. 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.
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 Soo Chin Lee ((65) 6779 5555, soo_chin_lee@nuhs.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rates of hypotension (time frame: For 48 hours since start of drainage). 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 NCT02811406, 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 23 Jun 2016.