Cardiovascular DiseasesPhase 4HERACLESNCT03280745
Hypertonic Saline for Fluid Resuscitation After Cardiac Surgery
A Phase 4 study testing Hypertonic saline and 0.9% saline in people with Cardiovascular Diseases and Valvular Heart Disease, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
Trial summary
Background: Volume replacement strategies and type of fluid used in patients undergoing cardiac surgery have changed during the last years. Currently used crystalloid solutes have a variable composition and a major impact on organ function and outcome. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiovascular Diseases, Valvular Heart Disease
- What is being tested?
- Hypertonic saline and 0.9% saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 165 participants
- Where
- 1 siteSwitzerland
- Study dates
- 27 Feb 2018to 30 Sep 2019
- Phase
- Phase 4
- 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
- Adult patients undergoing cardiac surgery for ischemic or valvular heart disease
Who cannot join
- Patients unable to give informed consent
- Patients with age <18 years
- Pregnancy or breastfeeding
- Left-ventricular ejection fraction (LVEF) < 30% preoperatively
- Preexisting renal insufficiency with an eGFR <30 ml/min/1.73m2
- Patients with postoperative circulatory support devices such as LVAD, IABP, Impella, ECMO
Show all 11Show fewer
- Preexisting serum sodium of >145mmol/l or <135 mmol/L
- Preexisting serum chloremia >107mmol/l or < 98 mmol/L
- Systemic steroid therapy (at any dose at time of inclusion)
- Chronic liver disease (bilirubin >3 mg.dl)
- Any signs of infection or sepsis defined as clear clinical evidence for active infection or current antibiotic therapy
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Department of Intensive Care, Bern University Hospital and University of Bern, Bern, Switzerland
Bern, 3010
About this study
Background: Volume replacement strategies and type of fluid used in patients undergoing cardiac surgery have changed during the last years. Currently used crystalloid solutes have a variable composition and a major impact on organ function and outcome. Additionally critically ill patients are prone to fluid overload, which is despite common perception, not a benign occurrence as it is associated with prolonged ICU- and hospital length of stay and increased mortality rates. Fluid resuscitation using bolus or continuous infusion of hypertonic saline was used for more than thirty years. Only a few studies have been conducted so far, but they showed that infusion of hypertonic saline results in less volume administered, increased renal function less weight gain in critically ill patients when compared to other crystalloids.
Aim: This preliminary randomized controlled double-blind study aims to identify whether fluid resuscitation using hypertonic saline (HS) when used in addition to lactated Ringers solution results in less total fluid amount administered in patients following cardiac surgery. Additionally we want to evaluate whether the use of hypertonic saline results less need for pharmacological cardiocirculatory support, increased renal function, less postoperative volume overload shortened post-cardiac bypass immune suppression and increased postoperative outcomes.
Study intervention: At admission to the ICU patients will receive 5ml/kg body weight of 7.3% NaCl or 0.9% NaCl by infusion pump over 60 minutes. If necessary, fluid resuscitation will thereafter be performed with Ringer's lactate to normalize peripheral perfusion and to allow weaning of vasopressors.
- Conditions
- Cardiovascular Diseases, Valvular Heart Disease
- Being tested
- Hypertonic saline, 0.9% saline
- Medical subject headings
- Cardiovascular Diseases, Heart Valve Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hypertonic salineDrug
Also called 7.9% NaCl
At admission to the ICU patients will receive 5ml/kg body weight of 7.3% NaCl by infusion pump over 60 minutes.
0.9% salineDrug
Also called normal saline
At admission to the ICU patients will receive 5ml/kg body weight of 0.9% NaCl by infusion pump over 60 minutes.
| Study group | Role | What they receive |
|---|---|---|
| 7.3% NaCl (intervention) | Active comparator | At admission to the ICU patients will receive 5ml/kg body weight of 7.3% NaCl NaCl by infusion pump over 60 minutes. Receives: Drug: Hypertonic saline |
| 0.9% NaCl (comparator) | Active comparator | At admission to the ICU patients will receive 5ml/kg body weight of 0.9% NaCl by infusion pump over 60 minutes. Receives: Drug: 0.9% saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
total cumulative amount of fluids infused
Measured: daily until ICU discharge, max until postoperative day 90
Secondary outcomes (12)
postoperative weight gain
Measured: until postoperative day 6
total postoperative cumulative urinary output
Measured: daily until ICU discharge, max until postoperative day 90
total cumulative dose of inopressors per kg bodyweight /hour
cumulation of norepinephrine and epinephrine
Measured: until ICU discharge, max until postoperative day 90
time on inopressors
norepinephrine and/or epinephrine
Measured: from ICU admission until stop of inopressors, max until postoperative day 90
variation in renal function markers
renal damage maker (TIMP2-IGFB, creatinine)
Measured: until postoperative day 6
variation in acid-base homeostasis
pH, base excess, lactate, bicarbonate, electrolytes
Measured: until postoperative day 6
variation in immune function
mHLA-DR
Measured: until postoperative day 6
time on the ventilator
Measured: from ICU admission until time of extubation, maximum 90 days
occurence of infection
Measured: occurence of infection during the index hospitalisation or subsequent admissions due to infection upto 90 postoperative days
length of stay
time to ICU/hospital-discharge
Measured: time to ICU/hospital-discharge however long this may take, maximum 90 days
readmissions to the ICU
Measured: readmissions to the ICU within postoperative 90 days
mortality
Measured: until postoperative day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2017
- Study start27 Feb 2018
- Primary completion27 May 2019
- Study completion30 Sep 2019
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 Cardiovascular DiseasesStudies 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- At admission to the ICU patients will receive 5ml/kg body weight of 7.3% NaCl or 0.9% NaCl by infusion pump over 60 minutes. If necessary, fluid resuscitation will be performed with Ringer's lactate to normalize peripheral perfusion and to allow weaning of vasopressors.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 165 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joerg C Schefold, MD, Study director, Department of Intensive Care, Inselspital, Bern University Hospital, Bern, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03280745
- Sponsor's protocol ID
- 201706011.1
- Acronym
- HERACLES
- Status last verified
- Mar 2020
- First submitted
- 23 Aug 2017
- Last updated
- 24 Mar 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pfortmueller CA, Messmer AS, Hess B, Reineke D, Jakob L, Wenger S, Waskowski J, Zuercher P, Stoehr F, Erdoes G, Luedi MM, Jakob SM, Englberger L, Schefold JC. Hypertonic saline for fluid resuscitation after cardiac surgery (HERACLES): study protocol for a preliminary randomised controlled clinical trial. Trials. 2019 Jun 14;20(1):357. doi: 10.1186/s13063-019-3420-6.
PubMed 31200756
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hypertonic Saline for Fluid Resuscitation After Cardiac Surgery
- ClinicalTrials.gov ID
- NCT03280745
- Acronym / sponsor ID
- HERACLES / 201706011.1
- Conditions
- Cardiovascular Diseases, Valvular Heart Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 165 participants (actual)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Study start
- 27 Feb 2018 (actual)
- Primary completion
- 27 May 2019 (actual)
- Study completion
- 30 Sep 2019 (actual)
- First posted
- 12 Sep 2017 (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.
Background: Volume replacement strategies and type of fluid used in patients undergoing cardiac surgery have changed during the last years. Currently used crystalloid solutes have a variable composition and a major impact on organ function and outcome. Additionally critically ill patients are prone to fluid overload, which is despite common perception, not a benign occurrence as it is associated with prolonged ICU- and hospital length of stay and increased mortality rates. Fluid resuscitation using bolus or continuous infusion of hypertonic saline was used for more than thirty years. Only a few studies have been conducted so far, but they showed that infusion of hypertonic saline results in less volume administered, increased renal function less weight gain in critically ill patients when compared to other crystalloids.
Aim: This preliminary randomized controlled double-blind study aims to identify whether fluid resuscitation using hypertonic saline (HS) when used in addition to lactated Ringers solution results in less total fluid amount administered in patients following cardiac surgery. Additionally we want to evaluate whether the use of hypertonic saline results less need for pharmacological cardiocirculatory support, increased renal function, less postoperative volume overload shortened post-cardiac bypass immune suppression and increased postoperative outcomes.
Study intervention: At admission to the ICU patients will receive 5ml/kg body weight of 7.3% NaCl or 0.9% NaCl by infusion pump over 60 minutes. If necessary, fluid resuscitation will thereafter be performed with Ringer's lactate to normalize peripheral perfusion and to allow weaning of vasopressors.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- At admission to the ICU patients will receive 5ml/kg body weight of 7.3% NaCl or 0.9% NaCl by infusion pump over 60 minutes. If necessary, fluid resuscitation will be performed with Ringer's lactate to normalize peripheral perfusion and to allow weaning of vasopressors.
| Arm | Type | Receives |
|---|---|---|
| 7.3% NaCl (intervention) | Active comparator | Drug: Hypertonic salineAt admission to the ICU patients will receive 5ml/kg body weight of 7.3% NaCl NaCl by infusion pump over 60 minutes. |
| 0.9% NaCl (comparator) | Active comparator | Drug: 0.9% salineAt admission to the ICU patients will receive 5ml/kg body weight of 0.9% NaCl by infusion pump over 60 minutes. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Adult patients undergoing cardiac surgery for ischemic or valvular heart disease
Key exclusion criteria (11 listed)
- Patients unable to give informed consent
- Patients with age <18 years
- Pregnancy or breastfeeding
- Left-ventricular ejection fraction (LVEF) < 30% preoperatively
- Preexisting renal insufficiency with an eGFR <30 ml/min/1.73m2
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 |
|---|---|---|
| Hypertonic salineAlso: 7.9% NaClAt admission to the ICU patients will receive 5ml/kg body weight of 7.3% NaCl by infusion pump over 60 minutes. | Drug | 7.3% NaCl (intervention) |
| 0.9% salineAlso: normal salineAt admission to the ICU patients will receive 5ml/kg body weight of 0.9% NaCl by infusion pump over 60 minutes. | Drug | 0.9% NaCl (comparator) |
Primary outcome
total cumulative amount of fluids infused
Time frame: daily until ICU discharge, max until postoperative day 90
12 secondary outcomes
postoperative weight gain
Time frame: until postoperative day 6
total postoperative cumulative urinary output
Time frame: daily until ICU discharge, max until postoperative day 90
total cumulative dose of inopressors per kg bodyweight /hour
Time frame: until ICU discharge, max until postoperative day 90
time on inopressors
Time frame: from ICU admission until stop of inopressors, max until postoperative day 90
variation in renal function markers
Time frame: until postoperative day 6
variation in acid-base homeostasis
Time frame: until postoperative day 6
variation in immune function
Time frame: until postoperative day 6
time on the ventilator
Time frame: from ICU admission until time of extubation, maximum 90 days
occurence of infection
Time frame: occurence of infection during the index hospitalisation or subsequent admissions due to infection upto 90 postoperative days
length of stay
Time frame: time to ICU/hospital-discharge however long this may take, maximum 90 days
readmissions to the ICU
Time frame: readmissions to the ICU within postoperative 90 days
mortality
Time frame: until postoperative day 90
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 24 Mar 2020.
- Derived from this study: PubMed 31200756Pfortmueller CA, Messmer AS, Hess B, Reineke D, Jakob L, Wenger S, Waskowski J, Zuercher P, Stoehr F, Erdoes G, Luedi MM, Jakob SM, Englberger L, Schefold JC. Hypertonic saline for fluid resuscitation after cardiac surgery (HERACLES): study protocol for a preliminary randomised controlled clinical trial. Trials. 2019 Jun 14;20(1):357. doi: 10.1186/s13063-019-3420-6.
- 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.
Joerg C Schefold, MD study director
Department of Intensive Care, Inselspital, Bern University Hospital, Bern, Switzerland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Hypertonic saline and 0.9% saline in people with Cardiovascular Diseases and Valvular Heart Disease, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
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 11 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 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 Switzerland. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
total cumulative amount of fluids infused (time frame: daily until ICU discharge, max until postoperative day 90). 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 NCT03280745, 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 2020.