Total Fluid Volume IncreasedNCT02361736
Evaluate the Nephrotoxicity by 6% Hydroxyethyl Starch 130/0.4 in Old Patients During Orthopaedic Surgery
A study testing Hydroxyethyl Starch and Lactate Ringers in people with Total Fluid Volume Increased, run by Yuanyuan Zhang at 1 site in China.
Trial summary
Hydroxyethyl starch (HES) is commonly used as plasma expander during surgery but may be nephrotoxic as seen in studies in patients with sepsis. The investigators hypothesized that the possible nephrotoxicity of 6% HES 130/0.4 could be revealed by measurements of urinary and plasma neutrophil gelatinase-associated… Read more about this study
- Who is it for?
- Ages 65 to 90 years
- Conditions the study is for
- Total Fluid Volume Increased
- What is being tested?
- Hydroxyethyl Starch and Lactate Ringers
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteChina
- Study dates
- Mar 2015to Jan 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 to 90 years
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Old patients scheduled to undergo orthopaedic surgery under a intravertebral anesthesia. (American Society of Anesthesiologists physical status I-Ⅲ)
Who cannot join
- Allergy and contraindication to HES
- Infections and malignancies
- Sepsis
- History of heart failure or New York Heart Association(NYHA)>Ⅲ
- Renal failure or Cr>108μmol/L，BUN>8.3mmol/L
- Undergoing dialytic treatments
Show all 9Show fewer
- Intracranial hemorrhages
- Taking non-steroidal antiinflammatory agent for a long time
- Inability to understand the Study Information Sheet and provide a written consent to take part in the study
Trial locations and contacts
1 site in 1 country.
China1 site
Tianjin Medical University General Hospital
Tianjin, Tianjin Municipality, 300052
About this study
Official title: Evaluate the Nephrotoxicity by 6% Hydroxyethyl Starch 130/0.4 in Old Patients
Hydroxyethyl starch (HES) is commonly used as plasma expander during surgery but may be nephrotoxic as seen in studies in patients with sepsis. The investigators hypothesized that the possible nephrotoxicity of 6% HES 130/0.4 could be revealed by measurements of urinary and plasma neutrophil gelatinase-associated lipocalin and interleukin-18 (IL-18) in old patients with normal renal function during orthopaedic surgery.
Read the detailed description
Hydroxyethyl starch (HES) is widely used as volume expander to maintain circulation in patients during surgery, trauma, and in critical disease, where a rapid and sustained volume expansion is the goal. However, acute kidney injury (AKI) is sometimes a complication in these patients and HES might be a contributing factor. Acute kidney injury is often diagnosed using a sudden rise in plasma creatinine (p-crea) or an abrupt decrease in urine output. P-crea depends on sex, nutrition, medication,muscle mass, and age and it increases 24 to 48 h after renal injury, so the diagnosis of AKI is delayed when using p-crea alone as an indicator for renal damage. New technology allows for earlier diagnosis of AKI using measurements of biomarkers in urine. Neutrophil gelatinase-associated lipocalin (NGAL) is a small protein, which is filtered via the glomeruli and reabsorbed in the proximal tubules, and thus low concentrations of NGAL can be measured in the blood and urine. Approximately 6 h after a renal injury, NGAL increases rapidly due to an up-regulated expression and secretion in the epithelial cells of the thick ascending limb of Henle's loop, the distal tubules, and the collecting ducts. Thus, NGAL can be used as a marker of renal damage. However, infections and malignancies can give falsely increased levels.
Interleukin-18 (IL-18) is mainly created from proximal kidney tubules which is a proinflammatory factor that can be detected in earlier urine of AKI animal models. There is significant rise in IL-18 levels in urine of AKI confirmed cases(no chronic kidney disease, no urinary tract infections, no prerenal factors), specificity and susceptibility is 90%. As a result, IL-18 can be selected as a biomarker.
Intravenously administrated HES is excreted in urine but is also partly accumulated in the tissues. Studies in animals and humans showed that HES molecules were accumulated in the proximal tubule cells with subsequent vacuolization and swelling-a condition known as osmotic nephrosis. However, recent studies, primarily conducted in patients with sepsis, found impaired renal function even when using tetrastarch. In contrast, perioperative studies found no evidence of AKI after infusion of HES. The investigators hypothesized that 6% HES 130/0.4 had a nephrotoxic effect, which could be revealed by measurements of urinary and plasma NGAL and IL-18; that 6% HES 130/0.4 influenced kidney function differently than crystalloids(lactated Ringer's solution) due to the different pharmacokinetic properties of colloids compared with that of crystalloids.
- Conditions
- Total Fluid Volume Increased
- Being tested
- Hydroxyethyl Starch, Lactate Ringers
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydroxyethyl StarchDrug
Also called HES
6% Hydroxyethyl Starch(HES) is intravenously given 7.5ml/kg for the first hour of surgery
Lactate RingersDrug
Also called LR
Lactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery
| Study group | Role | What they receive |
|---|---|---|
| Lactate Ringers | Sham comparator | Lactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery Receives: Drug: Lactate Ringers |
| Hydroxyethyl Starch | Experimental | 6% Hydroxyethyl Starch (HES) is intravenously administrated at a dose of 7.5ml/ kg in the first hour of surgery, and then, Lactate Ringers' is administrated to the patient until the end of the surgery Receives: Drug: Hydroxyethyl Starch |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentration of NGAL in Urine on 5 Time Point
Neutrophil gelatinase-associated lipocalin (NGAL) is a small protein, which is filtered via the glomeruli and reabsorbed in the proximal tubules, and thus low concentrations of NGAL can be measured in the blood and urine.
Measured: -1d, 0d, 1d, 3d, 5d after surgery
Concentration of IL-18 in Urine on 5 Time Point
IL-18 is mainly created from proximal kidney tubules which is a proinflammatory factor that can be detected in earlier urine of AKI animal models.
Measured: -1d, 0d, 1d, 3d, 5d after surgery
Concentration of IL-18 in Plasma on 5 Time Point
Measured: -1d, 0d, 1d, 3d, 5d after surgery
Concentration of NGAL in Plasma on 5 Time Point.
concentration of NGAL in plasma on 5 time point. Biomarkers are measured by ELISA.
Measured: -1d, 0d, 1d, 3d, 5d after surgery
Secondary outcomes (3)
Concentration of β2 Microglobulin in Urine
Measured: -1d, 0d, 1d, 3d, 5d after surgery
Estimated Glomerular Filtration Rate(eGFR) on 5 Time Point
eGFR is calculated by concentration of creatinine and CKD-EPI2009
Measured: -1d, 0d, 1d, 3d, 5d after surgery
Ratio of the Urine Trace Albumin and Creatinine(ACR) on 5 Time Point
ACR is calculated by the urine trace albumin divided by the urine creatinine
Measured: -1d, 0d, 1d, 3d, 5d after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2015 (estimated)
- Study startMar 2015
- Primary completionDec 2015
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Total Fluid Volume IncreasedStudies 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
- Interventional
- Phase
- Phase N/A
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yuanyuan Zhang
- Sponsor type
- University, hospital or other
- Collaborators
- Tianjin Union Medical Center, Tianjin First Central Hospital
- Responsible party
- Sponsor-investigator, Yuanyuan Zhang, Tianjin Medical University General Hospital
- Investigators
- Yu Yonghao, M.D.,Ph.D, Principal investigator, Tianjin Medical University General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02361736
- Sponsor's protocol ID
- IRB2014-102-01
- Status last verified
- Feb 2016
- First submitted
- 2 Feb 2015
- Last updated
- 24 Mar 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Zhang Y, Yu Y, Jia J, Yu W, Xu R, Geng L, Wei Y. Administration of HES in elderly patients undergoing hip arthroplasty under spinal anesthesia is not associated with an increase in renal injury. BMC Anesthesiol. 2017 Feb 21;17(1):29. doi: 10.1186/s12871-017-0320-8.
PubMed 28222674
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluate the Nephrotoxicity by 6% Hydroxyethyl Starch 130/0.4 in Old Patients
- ClinicalTrials.gov ID
- NCT02361736
- Acronym / sponsor ID
- IRB2014-102-01
- Conditions
- Total Fluid Volume Increased
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Yuanyuan ZhangUniversity, hospital or other
- Collaborators
- Tianjin Union Medical Center, Tianjin First Central Hospital
- Study start
- Mar 2015
- Primary completion
- Dec 2015 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 12 Feb 2015 (estimated)
- Results
- Posted 24 Mar 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hydroxyethyl starch (HES) is commonly used as plasma expander during surgery but may be nephrotoxic as seen in studies in patients with sepsis. The investigators hypothesized that the possible nephrotoxicity of 6% HES 130/0.4 could be revealed by measurements of urinary and plasma neutrophil gelatinase-associated lipocalin and interleukin-18 (IL-18) in old patients with normal renal function during orthopaedic surgery.
Detailed description
Hydroxyethyl starch (HES) is widely used as volume expander to maintain circulation in patients during surgery, trauma, and in critical disease, where a rapid and sustained volume expansion is the goal. However, acute kidney injury (AKI) is sometimes a complication in these patients and HES might be a contributing factor. Acute kidney injury is often diagnosed using a sudden rise in plasma creatinine (p-crea) or an abrupt decrease in urine output. P-crea depends on sex, nutrition, medication,muscle mass, and age and it increases 24 to 48 h after renal injury, so the diagnosis of AKI is delayed when using p-crea alone as an indicator for renal damage. New technology allows for earlier diagnosis of AKI using measurements of biomarkers in urine. Neutrophil gelatinase-associated lipocalin (NGAL) is a small protein, which is filtered via the glomeruli and reabsorbed in the proximal tubules, and thus low concentrations of NGAL can be measured in the blood and urine. Approximately 6 h after a renal injury, NGAL increases rapidly due to an up-regulated expression and secretion in the epithelial cells of the thick ascending limb of Henle's loop, the distal tubules, and the collecting ducts. Thus, NGAL can be used as a marker of renal damage. However, infections and malignancies can give falsely increased levels.
Interleukin-18 (IL-18) is mainly created from proximal kidney tubules which is a proinflammatory factor that can be detected in earlier urine of AKI animal models. There is significant rise in IL-18 levels in urine of AKI confirmed cases(no chronic kidney disease, no urinary tract infections, no prerenal factors), specificity and susceptibility is 90%. As a result, IL-18 can be selected as a biomarker.
Intravenously administrated HES is excreted in urine but is also partly accumulated in the tissues. Studies in animals and humans showed that HES molecules were accumulated in the proximal tubule cells with subsequent vacuolization and swelling-a condition known as osmotic nephrosis. However, recent studies, primarily conducted in patients with sepsis, found impaired renal function even when using tetrastarch. In contrast, perioperative studies found no evidence of AKI after infusion of HES. The investigators hypothesized that 6% HES 130/0.4 had a nephrotoxic effect, which could be revealed by measurements of urinary and plasma NGAL and IL-18; that 6% HES 130/0.4 influenced kidney function differently than crystalloids(lactated Ringer's solution) due to the different pharmacokinetic properties of colloids compared with that of crystalloids.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lactate Ringers | Sham comparator | Drug: Lactate RingersLactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery |
| Hydroxyethyl Starch | Experimental | Drug: Hydroxyethyl Starch6% Hydroxyethyl Starch (HES) is intravenously administrated at a dose of 7.5ml/ kg in the first hour of surgery, and then, Lactate Ringers' is administrated to the patient until the end of the surgery |
Who may qualify
- Ages
- 65 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (1 listed)
- Old patients scheduled to undergo orthopaedic surgery under a intravertebral anesthesia. (American Society of Anesthesiologists physical status I-Ⅲ)
Key exclusion criteria (9 listed)
- Allergy and contraindication to HES
- Infections and malignancies
- Sepsis
- History of heart failure or New York Heart Association(NYHA)>Ⅲ
- Renal failure or Cr>108μmol/L，BUN>8.3mmol/L
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 |
|---|---|---|
| Hydroxyethyl StarchAlso: HES6% Hydroxyethyl Starch(HES) is intravenously given 7.5ml/kg for the first hour of surgery | Drug | Hydroxyethyl Starch |
| Lactate RingersAlso: LRLactate Ringers is intravenously administrated at a dose of 7.5ml/kg during the surgery | Drug | Lactate Ringers |
Primary outcome
Concentration of NGAL in Urine on 5 Time Point
Time frame: -1d, 0d, 1d, 3d, 5d after surgery
Neutrophil gelatinase-associated lipocalin (NGAL) is a small protein, which is filtered via the glomeruli and reabsorbed in the proximal tubules, and thus low concentrations of NGAL can be measured in the blood and urine.
Concentration of IL-18 in Urine on 5 Time Point
Time frame: -1d, 0d, 1d, 3d, 5d after surgery
IL-18 is mainly created from proximal kidney tubules which is a proinflammatory factor that can be detected in earlier urine of AKI animal models.
Concentration of IL-18 in Plasma on 5 Time Point
Time frame: -1d, 0d, 1d, 3d, 5d after surgery
Concentration of NGAL in Plasma on 5 Time Point.
Time frame: -1d, 0d, 1d, 3d, 5d after surgery
concentration of NGAL in plasma on 5 time point. Biomarkers are measured by ELISA.
3 secondary outcomes
Concentration of β2 Microglobulin in Urine
Time frame: -1d, 0d, 1d, 3d, 5d after surgery
Estimated Glomerular Filtration Rate(eGFR) on 5 Time Point
Time frame: -1d, 0d, 1d, 3d, 5d after surgery
Ratio of the Urine Trace Albumin and Creatinine(ACR) on 5 Time Point
Time frame: -1d, 0d, 1d, 3d, 5d after surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28222674Zhang Y, Yu Y, Jia J, Yu W, Xu R, Geng L, Wei Y. Administration of HES in elderly patients undergoing hip arthroplasty under spinal anesthesia is not associated with an increase in renal injury. BMC Anesthesiol. 2017 Feb 21;17(1):29. doi: 10.1186/s12871-017-0320-8.
- Individual participant dataSharing planned: Undecided
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.
Yu Yonghao, M.D.,Ph.D principal investigator
Tianjin Medical University General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hydroxyethyl Starch and Lactate Ringers in people with Total Fluid Volume Increased, run by Yuanyuan Zhang at 1 site in China.
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 9 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 24 Mar 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 China. 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?
Yes. Results are posted in the registry (first posted 24 Mar 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Concentration of NGAL in Urine on 5 Time Point (time frame: -1d, 0d, 1d, 3d, 5d after 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 NCT02361736, 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 24 Mar 2016.