Fluid Retention TissueNCT04780490
Comparison of Liberal and Restrictive Fluid Management on the Endothelial Glycocalyx in Radical Cystectomy
A study testing liberal fluid management and restrictive fluid management in people with Fluid Retention Tissue, run by Istanbul University at 1 site in Turkey (Türkiye).
Trial summary
The aim of this study is to compare the effect of the liberal and restrictive fluid treatments which are routinely performed in major urological surgeries in the perioperative period on ANP release and the endothelial glycocalyx layer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fluid Retention Tissue
- What is being tested?
- liberal fluid management and restrictive fluid management
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 1 Mar 2018to 1 Apr 2021
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ASA (The American Society of Anesthesiologists) status I-II-III patients
- Cases undergoing major urological surgery
- Cases for invasive artery monitoring and central venous catheterization
- Patients receiving general anesthesia
- Volunteering to participate in the study
Who cannot join
- Coagulopathy
- Patients with severe heart, kidney and liver dysfunction (EF <35% and / or GFR <30, Cre:> 2.5 and / or impaired liver function tests)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Comparison of the Effects of Perioperative Liberal and Restrictive Fluid Management on the Endothelial Glycocalyx Layer in Radical Cystectomy and Urinary Diversion
The aim of this study is to compare the effect of the liberal and restrictive fluid treatments which are routinely performed in major urological surgeries in the perioperative period on ANP release and the endothelial glycocalyx layer.
In the study, the investigators aimed to compare changes in the glycocalyx structure by measuring the blood levels of ANP and heparan sulfate, hyaluronan and syndecan 1, which form the glycocalyx structure on the patients who received the liberal and restrictive fluid treatments during major urological surgeries.
Read the detailed description
There is no strong evidence about the optimal fluid resuscitation for the patients undergoing major surgeries. Avoiding excess fluid resuscitation in the perioperative period is essential for reducing postoperative complications, morbidity and long-term mortality. In the perioperative period, ANP is released with increased wall stress in the cardiac atrium due to excess fluid loading. With the release of ANP, damage occurs in the glycocalyx layer, which is the structure primarily responsible for the permeability in the vascular endothelium.
Thus, the amount of ANP released from atrium and heparan sulfate, syndecan 1, hyaluronan in the glycocalyx layer structure increases in the blood.
The aim of this study is to compare changes in the glycocalyx structure by measuring the blood levels of ANP and heparan sulfate, hyaluronan and syndecan 1, which form the glycocalyx structure on the patients who received the liberal and restrictive fluid treatments during major urological surgeries. The blood samples will be taken at the beginning and at the end of the surgery.
The primary outcome of this study is the increase in ANP levels and heparan sulfate , hyaluronic acid, syndecan 1 levels which are the glycocalyx damage products in blood.
Secondary outcomes are intraoperative advanced hemodynamic cardiac measurement values, the amount of blood and blood products replaced to patients, duration of intensive care stay, duration of hospital stay, cardiac and respiratory complications, gastrointestinal complications, urinary complications, surgical complications such as anastomotic leaks, wound infection and fistula.
- Conditions
- Fluid Retention Tissue
- Being tested
- liberal fluid management, restrictive fluid management
- Keywords
- peroperative fluid management, restrictive fluid therapy, endothelial glycocalyx, Liberal fluid therapy
- Medical subject headings
- Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
liberal fluid managementOther
10 ml/ kg/ hr Ringer's lactate solution
restrictive fluid managementOther
2 ml/ kg/ hr Ringer's lactate solution with 2 mcg / kg / hr norepinephrine infusion
| Study group | Role | What they receive |
|---|---|---|
| liberal fluid therapy | Active comparator | Patients will be applied 2 mg midazolam for premedication. Before anesthesia induction, epidural catheter will be inserted to all patients and test dose will be made with 3 cc % 2 lidocaine (No medication from the epidural catheter will be administered during surgery).
Standard anesthesia induction will be applied (fentanyl 2 mcg/kg; propofol 2 mg/kg; rocuronium 0.6 mg/kg ), and after intubation maintenance of anesthesia will be achieved with sevoflurane with a minimum alveolar concentration (MAC) of 0.8-1.
Fluid resuscitation will be started with 10 ml / kg / hr Ringer's lactate solution.
In patients with MAP <65 mmHg, 250 ml of Ringer's lactate solution will be given as a bolus.
If the hypotension persists, the bolus 250 ml Ringer's lactate solution will be repeated up to 10 times. Receives: Other: liberal fluid management |
| restrictive fluid therapy | Active comparator | Patients will be applied 2 mg midazolam for premedication. Before anesthesia induction, epidural catheter will be inserted to all patients and test dose will be made with 3 cc % 2 lidocaine ( No medication from the epidural catheter will be administered during surgery. ) Standard anesthesia induction will be applied ( fentanyl 2 mcg/kg; propofol 2 mg/kg; rocuronium 0.6 mg/kg ) and after intubation maintenance of anesthesia will be achieved with sevoflurane with a minimum alveolar concentration (MAC) of 0.8-1.
Fluid resuscitation will be started with 2 ml / kg / hr Ringer's lactate solution and norepinephrine infusion at a dose of 2 mcg / kg / hr.
In patients with MAP<65 mmHg, norepinephrine dose will be increased up to 8 mcg / kg / hr.
If the hypotension persists although the norepinephrine dose is 8 mcg / kg / hr, 250 ml bolus Ringer's lactate solution will be given. Receives: Other: restrictive fluid management |
What is being measured
The primary outcome is the main question the study is designed to answer.
Atrial Natriuretic Peptide (ANP)( pg/mL)
Blood ANP concentration will be determined using an enzyme-linked immunosorbent assay kit
Measured: The blood sample will be taken at beginning and end of the surgery
Heparan sulfate (ng/L)
Blood Heparan sulfate concentration will determine using an enzyme-linked immunosorbent assay kit
Measured: The blood sample will be taken at beginning and end of the surgery
Syndecan 1 (pg/mL)
Blood Syndecan 1 concentration will be determined using an enzyme-linked immunosorbent
Measured: The blood sample will be taken at beginning and end of the surgery
Hyaluronan (ng/L)
Blood Hyaluronan concentration will be determined using an enzyme-linked immunosorbent
Measured: The blood sample will be taken at beginning and end of the surgery
Secondary outcomes (12)
Amount of blood transfusion (unit)
Including red cell, fresh frozen plasma
Measured: From the beginning surgery to day 2 postoperatively
Total intensive care unit (ICU) stay (Hour, day)
Including initial ICU admission and readmission times
Measured: 30 days postoperative
Hospital stay (Hour, day)
From the beginning of surgery until actual hospital discharge
Measured: 90 days postoperative
Gastrointestinal complications
Ileus, constipation, gastrointestinal bleeding, gastric ulcer, anastomotic intestinal leakage
Measured: 30 days postoperative
Infectious complications
Urinary tract infection, pyelonephritis, urosepsis, pneumonia, wound infection
Measured: 30 days postoperative
Surgical site complications
Wound dehiscence, evisceration
Measured: 30 days postoperative
Genitourinary complications
Acute kidney injury, urethral anastamosis leak
Measured: 30 days postoperative
Cardiac complications
Acute myocardial infarction, congestive heart failure, arrhythmia
Measured: 30 days postoperative
Thromboembolic complications
pulmonary embolism
Measured: 30 days postoperative
Stroke Volume Variation (SVV)(%)
SVV will be measured with Flo-Trac system (Edward Life Sciences). Normal range is about %10-15
Measured: From onset of the surgery up to end of the surgery, every 30 minutes
Cardiac Index(CI )(l min-1 m-2),
CI will be measured with Flo-Trac system (Edward Life Sciences). Normal value is 2,6-4,2 l min-1 m-2
Measured: From onset of the surgery up to end of the surgery, every 30 minutes
Systemic Vascular Resistance Index (SVRI )(dyn*s.cm-5 )
SVRI will be measured with Flo-Trac system (Edward Life Sciences). Normal value is about 900-1300 dyn*s.cm-5
Measured: From onset of the surgery up to end of the surgery, every 30 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2021
- Study start1 Mar 2018
- Primary completion15 Mar 2021
- Study completion1 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fluid Retention TissueStudies of the same condition, open and under way.
- More trials run by Istanbul UniversityThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istanbul University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Meltem Savran Karadeniz, Istanbul University
- Investigators
- Meltem Savran KARADENİZ, Principal investigator, Istanbul University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04780490
- Sponsor's protocol ID
- 2018/374
- Status last verified
- Mar 2022
- First submitted
- 6 Feb 2020
- Last updated
- 29 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Kivanc D, Oztan G, Senturk Ciftci H, Karadeniz ST, Oguz SR, Kulaksiz Mammadov B, Savran Karadeniz M. Effects of perioperative fluid management on Glycocalyx injury in major urological oncology surgeries: a genetics and bioinformatics based approach. J Investig Med. 2026 Apr 10:10815589261444732. doi: 10.1177/10815589261444732. Online ahead of print.
PubMed 41964253
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of the Effects of Perioperative Liberal and Restrictive Fluid Management on the Endothelial Glycocalyx Layer in Radical Cystectomy and Urinary Diversion
- ClinicalTrials.gov ID
- NCT04780490
- Acronym / sponsor ID
- 2018/374
- Conditions
- Fluid Retention Tissue
- Keywords
- peroperative fluid management, restrictive fluid therapy, endothelial glycocalyx, Liberal fluid therapy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Istanbul UniversityUniversity, hospital or other
- Study start
- 1 Mar 2018 (actual)
- Primary completion
- 15 Mar 2021 (actual)
- Study completion
- 1 Apr 2021 (actual)
- First posted
- 3 Mar 2021 (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.
The aim of this study is to compare the effect of the liberal and restrictive fluid treatments which are routinely performed in major urological surgeries in the perioperative period on ANP release and the endothelial glycocalyx layer.
In the study, the investigators aimed to compare changes in the glycocalyx structure by measuring the blood levels of ANP and heparan sulfate, hyaluronan and syndecan 1, which form the glycocalyx structure on the patients who received the liberal and restrictive fluid treatments during major urological surgeries.
Detailed description
There is no strong evidence about the optimal fluid resuscitation for the patients undergoing major surgeries. Avoiding excess fluid resuscitation in the perioperative period is essential for reducing postoperative complications, morbidity and long-term mortality. In the perioperative period, ANP is released with increased wall stress in the cardiac atrium due to excess fluid loading. With the release of ANP, damage occurs in the glycocalyx layer, which is the structure primarily responsible for the permeability in the vascular endothelium.
Thus, the amount of ANP released from atrium and heparan sulfate, syndecan 1, hyaluronan in the glycocalyx layer structure increases in the blood.
The aim of this study is to compare changes in the glycocalyx structure by measuring the blood levels of ANP and heparan sulfate, hyaluronan and syndecan 1, which form the glycocalyx structure on the patients who received the liberal and restrictive fluid treatments during major urological surgeries. The blood samples will be taken at the beginning and at the end of the surgery.
The primary outcome of this study is the increase in ANP levels and heparan sulfate , hyaluronic acid, syndecan 1 levels which are the glycocalyx damage products in blood.
Secondary outcomes are intraoperative advanced hemodynamic cardiac measurement values, the amount of blood and blood products replaced to patients, duration of intensive care stay, duration of hospital stay, cardiac and respiratory complications, gastrointestinal complications, urinary complications, surgical complications such as anastomotic leaks, wound infection and fistula.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| liberal fluid therapy | Active comparator | Other: liberal fluid managementPatients will be applied 2 mg midazolam for premedication. Before anesthesia induction, epidural catheter will be inserted to all patients and test dose will be made with 3 cc % 2 lidocaine (No medication from the epidural catheter will be administered during surgery). Standard anesthesia induction will be applied (fentanyl 2 mcg/kg; propofol 2 mg/kg; rocuronium 0.6 mg/kg ), and after intubation maintenance of anesthesia will be achieved with sevoflurane with a minimum alveolar concentration (MAC) of 0.8-1. Fluid resuscitation will be started with 10 ml / kg / hr Ringer's lactate solution. In patients with MAP <65 mmHg, 250 ml of Ringer's lactate solution will be given as a bolus. If the hypotension persists, the bolus 250 ml Ringer's lactate solution will be repeated up to 10 times. |
| restrictive fluid therapy | Active comparator | Other: restrictive fluid managementPatients will be applied 2 mg midazolam for premedication. Before anesthesia induction, epidural catheter will be inserted to all patients and test dose will be made with 3 cc % 2 lidocaine ( No medication from the epidural catheter will be administered during surgery. ) Standard anesthesia induction will be applied ( fentanyl 2 mcg/kg; propofol 2 mg/kg; rocuronium 0.6 mg/kg ) and after intubation maintenance of anesthesia will be achieved with sevoflurane with a minimum alveolar concentration (MAC) of 0.8-1. Fluid resuscitation will be started with 2 ml / kg / hr Ringer's lactate solution and norepinephrine infusion at a dose of 2 mcg / kg / hr. In patients with MAP<65 mmHg, norepinephrine dose will be increased up to 8 mcg / kg / hr. If the hypotension persists although the norepinephrine dose is 8 mcg / kg / hr, 250 ml bolus Ringer's lactate solution will be given. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- ASA (The American Society of Anesthesiologists) status I-II-III patients
- Cases undergoing major urological surgery
- Cases for invasive artery monitoring and central venous catheterization
- Patients receiving general anesthesia
- Volunteering to participate in the study
Key exclusion criteria (2 listed)
- Coagulopathy
- Patients with severe heart, kidney and liver dysfunction (EF <35% and / or GFR <30, Cre:> 2.5 and / or impaired liver function tests)
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 |
|---|---|---|
| liberal fluid management10 ml/ kg/ hr Ringer's lactate solution | Other | liberal fluid therapy |
| restrictive fluid management2 ml/ kg/ hr Ringer's lactate solution with 2 mcg / kg / hr norepinephrine infusion | Other | restrictive fluid therapy |
Primary outcome
Atrial Natriuretic Peptide (ANP)( pg/mL)
Time frame: The blood sample will be taken at beginning and end of the surgery
Blood ANP concentration will be determined using an enzyme-linked immunosorbent assay kit
Heparan sulfate (ng/L)
Time frame: The blood sample will be taken at beginning and end of the surgery
Blood Heparan sulfate concentration will determine using an enzyme-linked immunosorbent assay kit
Syndecan 1 (pg/mL)
Time frame: The blood sample will be taken at beginning and end of the surgery
Blood Syndecan 1 concentration will be determined using an enzyme-linked immunosorbent
Hyaluronan (ng/L)
Time frame: The blood sample will be taken at beginning and end of the surgery
Blood Hyaluronan concentration will be determined using an enzyme-linked immunosorbent
12 secondary outcomes
Amount of blood transfusion (unit)
Time frame: From the beginning surgery to day 2 postoperatively
Total intensive care unit (ICU) stay (Hour, day)
Time frame: 30 days postoperative
Hospital stay (Hour, day)
Time frame: 90 days postoperative
Gastrointestinal complications
Time frame: 30 days postoperative
Infectious complications
Time frame: 30 days postoperative
Surgical site complications
Time frame: 30 days postoperative
Genitourinary complications
Time frame: 30 days postoperative
Cardiac complications
Time frame: 30 days postoperative
Thromboembolic complications
Time frame: 30 days postoperative
Stroke Volume Variation (SVV)(%)
Time frame: From onset of the surgery up to end of the surgery, every 30 minutes
Cardiac Index(CI )(l min-1 m-2),
Time frame: From onset of the surgery up to end of the surgery, every 30 minutes
Systemic Vascular Resistance Index (SVRI )(dyn*s.cm-5 )
Time frame: From onset of the surgery up to end of the surgery, every 30 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 29 Mar 2022.
- Derived from this study: PubMed 41964253Kivanc D, Oztan G, Senturk Ciftci H, Karadeniz ST, Oguz SR, Kulaksiz Mammadov B, Savran Karadeniz M. Effects of perioperative fluid management on Glycocalyx injury in major urological oncology surgeries: a genetics and bioinformatics based approach. J Investig Med. 2026 Apr 10:10815589261444732. doi: 10.1177/10815589261444732. Online ahead of print.
- Restrictive deferred hydration combined with preemptive norepinephrine infusion during radical cystectomy reduces postoperative complications and hospitalization time: a randomized clinical trial.Link provided by the sponsor.
- Hypervolemia increases release of atrial natriuretic peptide and shedding of the endothelial glycocalyx.Link provided by the sponsor.
- Revised Starling equation and the glycocalyx model of transvascular fluid exchange: an improved paradigm for prescribing intravenous fluid therapyLink provided by the sponsor.
Related trials for Fluid Retention Tissue
Recruiting
Transitional Care Program for Fluid Overload in Cirrhosis
Cirrhosis, Liver
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.
Meltem Savran KARADENİZ principal investigator
Istanbul University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing liberal fluid management and restrictive fluid management in people with Fluid Retention Tissue, run by Istanbul University at 1 site in Turkey (Türkiye).
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 5 inclusion and 2 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 29 Mar 2022. 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 Turkey (Türkiye). 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?
Atrial Natriuretic Peptide (ANP)( pg/mL) (time frame: The blood sample will be taken at beginning and end of the surgery). The study lists 4 primary outcomes in all. 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 NCT04780490, which also lists 1 linked publication.
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 29 Mar 2022.