ShockNCT04303455
Renin as a Biomarker of Haemodynamic Normalisation
An observational study of Shock, run by South West Sydney Local Health District at 1 site in Australia.
Trial summary
Study design Observational, single centre, prospective cohort study Planned sample size 100 participants Inclusion criteria The study will evaluate a cohort of participants meeting the following inclusion criteria: 1. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Shock
- What is being tested?
- blood sampling
- How many people
- 104 participants
- Where
- 1 siteAustralia
- Study dates
- 24 Mar 2020to 12 Mar 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Admission to ICU after elective and emergency cardiac surgery following cardiopulmonary bypass
Who may be able to join
- Admission to ICU after elective and emergency cardiac surgery following cardiopulmonary bypass
- Age 18 years and above
- Arterial, central venous catheters and pulmonary arterial catheters are inserted preoperatively
Who cannot join
- Age under 18 years
- Known pregnancy
- Arterial, central venous catheters and pulmonary arterial catheters that are not indicated as part of routine care
- End stage renal disease requiring renal replacement therapy
- Participants with known Child Pugh A cirrhosis or greater
- Treatment with any steroids
- Participant is not expected to live beyond the day after the day of admission
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Renin as a Biomarker of Haemodynamic Normalisation: Associations With Outcomes After Cardiac Surgery
Study design Observational, single centre, prospective cohort study Planned sample size 100 participants
Inclusion criteria The study will evaluate a cohort of participants meeting the following inclusion criteria:
- admission to the Intensive Care Unit (ICU) after elective and emergency cardiac surgery using cardiopulmonary bypass
- age 18 years and above
- arterial, central venous and pulmonary arterial catheters have been inserted as part of routine care Study procedures In addition to routine clinical postoperative data and blood collection, serum renin levels will be analysed on admission, 6 and 24 hours after admission to ICU Study duration 6 months
Read the detailed description
The renin-angiotensin aldosterone system (RAAS) is integral to cardiovascular homeostasis and involved in the regulation of blood pressure, electrolyte balance and intravascular volume. Renin is produced from the renal juxtaglomerular cells and converts angiotensinogen to angiotensin. Angiotensin is subsequently converted to angiotensin II by angiotensin-converting enzyme (ACE). Angiotensin II also promotes the release of aldosterone.The RAAS has an important role in hypotension to retain water through aldosterone and increase systemic vascular resistance mainly through angiotensin II but also through the release of vasopressin.
The RAAS can become dysregulated in critically ill shocked patients. In states such as septic shock the effects of the RAAS are antagonized through the production of vasodilators such a nitric oxide and both angiotensin I and angiotensin II receptors are down regulated. Activation of angiotensin I receptors may furthermore result in the production of pro-inflammatory cytokines that results in further vasodilation and contributes to cardiovascular compromise.
While the RAAS has been extensively investigated in cardiovascular patients there is a paucity of studies relevant to ICU. A recent study suggested that raised serum renin levels in patients with sepsis is associated with acute renal failure. Another study of a small heterogeneous cohort of critically ill patients compared renin to lactate as marker of tissue perfusion.
As RAAS is closely related to the volume state, there is a physiological rationale to investigate serum renin levels together with variables to monitor the intravascular volume, including assessment of the mean systemic filling pressure (Pmsf). An analogue of the Pmsf will be calculated in this study based on routine postoperative haemodynamic monitoring (mean arterial pressure, MAP, central venous pressure, CVP, cardiac output, CO).
Furthermore, there is no current research which looks at serum renin as marker of hemodynamic normalization or association with outcomes after cardiac surgery which is the main purpose of this study.
Serum renin as a candidate sensitive biomarker of hemodynamic homeostasis will be compared to current clinical markers of resuscitation and perfusion including cardiac index, mixed venous oxygen saturation, lactate and venoarterial carbon dioxide gradients.
If the serum renin concentration is found to be a marker of resuscitation and hemodynamic status, the study will examine any associations with lack of hemodynamic normalization and morbidity in cardiothoracic patients. A pragmatic, composite morbidity outcome at 30 days will be used as the primary endpoint. This includes renal impairment, myocardial infarction, persistent cardiogenic shock, arrythmia, respiratory failure, delirium and stroke. An exploratory, secondary outcome will focus on whether serum renin concentrations are associated with acute kidney injury and the need of renal replacement therapy in post cardiac surgical patients.
- Conditions
- Shock
- Being tested
- blood sampling
- Keywords
- Biomarkers of shock, Biomarkers of adverse outcomes in shocked patients, Biomarkers of adverse outcomes in cardiothoracic patients
- Medical subject headings
- Shock
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood samplingDiagnostic test
sampling serum renin
| Study group | Role | What they receive |
|---|---|---|
| Study group | The study will evaluate a cohort of participants meeting the following inclusion criteria:
1. Admission to ICU after elective and emergency cardiac surgery following cardiopulmonary bypass
2. Age 18 years and above
3. Arterial, central venous and pulmonary arterial catheters have been inserted as part of routine care
Data collection, serum renin among routine blood collection on admission, 6 and 24 hours after admission to ICU Receives: Diagnostic Test: blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patterns of changes in serum renin concentrations are associated with composite morbidity at 30 days in participants who have undergone cardiac surgery.
Measured: 30 days
Secondary outcomes (3)
Patterns of changes in serum renin concentrations correlate with current markers of resuscitation in participants who have undergone cardiac surgery ( C.I, SvO2, MAP, urine output, serum lactate, based deficit, venoarterial CO2 gradients)
Measured: 24 hours
Serum renin concentrations correlate with Pmsa in postoperative cardiac surgical patients
Measured: 24 hours
Patterns of changes in serum renin concentrations are associated with AKI or the need for CRRT in participants who have undergone cardiac surgery
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2020
- Study start24 Mar 2020
- Primary completion15 Feb 2021
- Study completion12 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for ShockStudies 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
- 104 participants (actual)
Sponsor and investigators
- Lead sponsor
- South West Sydney Local Health District
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anders Aneman, South West Sydney Local Health District
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04303455
- Sponsor's protocol ID
- 2019/PID15341
- Status last verified
- Mar 2021
- First submitted
- 8 Mar 2020
- Last updated
- 24 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Results of the study will be shared
Publications
Nguyen M, Denimal D, Dargent A, Guinot PG, Duvillard L, Quenot JP, Bouhemad B. Plasma Renin Concentration is Associated With Hemodynamic Deficiency and Adverse Renal Outcome in Septic Shock. Shock. 2019 Oct;52(4):e22-e30. doi: 10.1097/SHK.0000000000001285.
PubMed 30407370Myles PS. Meaningful outcome measures in cardiac surgery. J Extra Corpor Technol. 2014 Mar;46(1):23-7.
PubMed 24779115Hall A, Busse LW, Ostermann M. Angiotensin in Critical Care. Crit Care. 2018 Mar 20;22(1):69. doi: 10.1186/s13054-018-1995-z.
PubMed 29558991Khanna AK. Tissue Perfusion and Prognosis in the Critically Ill-Is Renin the New Lactate? Crit Care Med. 2019 Feb;47(2):288-290. doi: 10.1097/CCM.0000000000003582. No abstract available.
PubMed 30653057
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Renin as a Biomarker of Haemodynamic Normalisation: Associations With Outcomes After Cardiac Surgery
- ClinicalTrials.gov ID
- NCT04303455
- Acronym / sponsor ID
- 2019/PID15341
- Conditions
- Shock
- Keywords
- Biomarkers of shock, Biomarkers of adverse outcomes in shocked patients, Biomarkers of adverse outcomes in cardiothoracic patients
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 104 participants (actual)
- Lead sponsor
- South West Sydney Local Health DistrictUniversity, hospital or other
- Study start
- 24 Mar 2020 (actual)
- Primary completion
- 15 Feb 2021 (actual)
- Study completion
- 12 Mar 2021 (actual)
- First posted
- 11 Mar 2020 (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.
Study design Observational, single centre, prospective cohort study Planned sample size 100 participants
Inclusion criteria The study will evaluate a cohort of participants meeting the following inclusion criteria:
- admission to the Intensive Care Unit (ICU) after elective and emergency cardiac surgery using cardiopulmonary bypass
- age 18 years and above
- arterial, central venous and pulmonary arterial catheters have been inserted as part of routine care Study procedures In addition to routine clinical postoperative data and blood collection, serum renin levels will be analysed on admission, 6 and 24 hours after admission to ICU Study duration 6 months
Detailed description
The renin-angiotensin aldosterone system (RAAS) is integral to cardiovascular homeostasis and involved in the regulation of blood pressure, electrolyte balance and intravascular volume. Renin is produced from the renal juxtaglomerular cells and converts angiotensinogen to angiotensin. Angiotensin is subsequently converted to angiotensin II by angiotensin-converting enzyme (ACE). Angiotensin II also promotes the release of aldosterone.The RAAS has an important role in hypotension to retain water through aldosterone and increase systemic vascular resistance mainly through angiotensin II but also through the release of vasopressin.
The RAAS can become dysregulated in critically ill shocked patients. In states such as septic shock the effects of the RAAS are antagonized through the production of vasodilators such a nitric oxide and both angiotensin I and angiotensin II receptors are down regulated. Activation of angiotensin I receptors may furthermore result in the production of pro-inflammatory cytokines that results in further vasodilation and contributes to cardiovascular compromise.
While the RAAS has been extensively investigated in cardiovascular patients there is a paucity of studies relevant to ICU. A recent study suggested that raised serum renin levels in patients with sepsis is associated with acute renal failure. Another study of a small heterogeneous cohort of critically ill patients compared renin to lactate as marker of tissue perfusion.
As RAAS is closely related to the volume state, there is a physiological rationale to investigate serum renin levels together with variables to monitor the intravascular volume, including assessment of the mean systemic filling pressure (Pmsf). An analogue of the Pmsf will be calculated in this study based on routine postoperative haemodynamic monitoring (mean arterial pressure, MAP, central venous pressure, CVP, cardiac output, CO).
Furthermore, there is no current research which looks at serum renin as marker of hemodynamic normalization or association with outcomes after cardiac surgery which is the main purpose of this study.
Serum renin as a candidate sensitive biomarker of hemodynamic homeostasis will be compared to current clinical markers of resuscitation and perfusion including cardiac index, mixed venous oxygen saturation, lactate and venoarterial carbon dioxide gradients.
If the serum renin concentration is found to be a marker of resuscitation and hemodynamic status, the study will examine any associations with lack of hemodynamic normalization and morbidity in cardiothoracic patients. A pragmatic, composite morbidity outcome at 30 days will be used as the primary endpoint. This includes renal impairment, myocardial infarction, persistent cardiogenic shock, arrythmia, respiratory failure, delirium and stroke. An exploratory, secondary outcome will focus on whether serum renin concentrations are associated with acute kidney injury and the need of renal replacement therapy in post cardiac surgical patients.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study group | – | Diagnostic Test: blood samplingThe study will evaluate a cohort of participants meeting the following inclusion criteria: 1. Admission to ICU after elective and emergency cardiac surgery following cardiopulmonary bypass 2. Age 18 years and above 3. Arterial, central venous and pulmonary arterial catheters have been inserted as part of routine care Data collection, serum renin among routine blood collection on admission, 6 and 24 hours after admission to ICU |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Admission to ICU after elective and emergency cardiac surgery following cardiopulmonary bypass
Key inclusion criteria (3 listed)
- Admission to ICU after elective and emergency cardiac surgery following cardiopulmonary bypass
- Age 18 years and above
- Arterial, central venous catheters and pulmonary arterial catheters are inserted preoperatively
Key exclusion criteria (7 listed)
- Age under 18 years
- Known pregnancy
- Arterial, central venous catheters and pulmonary arterial catheters that are not indicated as part of routine care
- End stage renal disease requiring renal replacement therapy
- Participants with known Child Pugh A cirrhosis or greater
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 |
|---|---|---|
| blood samplingsampling serum renin | Diagnostic test | Study group |
Primary outcome
Patterns of changes in serum renin concentrations are associated with composite morbidity at 30 days in participants who have undergone cardiac surgery.
Time frame: 30 days
3 secondary outcomes
Patterns of changes in serum renin concentrations correlate with current markers of resuscitation in participants who have undergone cardiac surgery ( C.I, SvO2, MAP, urine output, serum lactate, based deficit, venoarterial CO2 gradients)
Time frame: 24 hours
Serum renin concentrations correlate with Pmsa in postoperative cardiac surgical patients
Time frame: 24 hours
Patterns of changes in serum renin concentrations are associated with AKI or the need for CRRT in participants who have undergone cardiac surgery
Time frame: 30 days
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 2021.
- Background: PubMed 30407370Nguyen M, Denimal D, Dargent A, Guinot PG, Duvillard L, Quenot JP, Bouhemad B. Plasma Renin Concentration is Associated With Hemodynamic Deficiency and Adverse Renal Outcome in Septic Shock. Shock. 2019 Oct;52(4):e22-e30. doi: 10.1097/SHK.0000000000001285.
- Background: PubMed 24779115Myles PS. Meaningful outcome measures in cardiac surgery. J Extra Corpor Technol. 2014 Mar;46(1):23-7.
- Results publication: PubMed 29558991Hall A, Busse LW, Ostermann M. Angiotensin in Critical Care. Crit Care. 2018 Mar 20;22(1):69. doi: 10.1186/s13054-018-1995-z.
- Results publication: PubMed 30653057Khanna AK. Tissue Perfusion and Prognosis in the Critically Ill-Is Renin the New Lactate? Crit Care Med. 2019 Feb;47(2):288-290. doi: 10.1097/CCM.0000000000003582. No abstract available.
- Individual participant dataSharing planned: No. Results of the study will be shared
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Shock, run by South West Sydney Local Health District at 1 site in Australia.
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 3 inclusion and 7 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 2021. 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 Australia. 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?
Patterns of changes in serum renin concentrations are associated with composite morbidity at 30 days in participants who have undergone cardiac surgery. (time frame: 30 days). 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 NCT04303455, which also lists 4 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 24 Mar 2021.