PediatricsNCT02728128
Platelet and Tissue cAMP: Novel Biomarkers of Milrinone Efficacy in Children
An observational study of Pediatrics and Heart Failure, run by University of Colorado, Denver at 1 site in United States.
Trial summary
The purpose of this study is to identify if circulating platelet cyclic adenosine monophosphate (cAMP) levels can be used as a biomarker of milrinone efficacy in children following cardiac surgery or undergoing heart transplant. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Pediatrics, Heart Failure, Congenital Heart Disease
- How many people
- 53 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2016to 17 Aug 2017
- 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 Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Children undergoing cardiac surgery with the use of cardiopulmonary bypass
Who may be able to join
- Children aged birth to 18 year of age
- Surgical complexity STAT score > 3
- Use of cardiopulmonary bypass for cardiac surgery
- Use of milrinone intra-operatively and post-operatively
Who cannot join
- Patients on milrinone therapy prior to surgery
- Gestational age less than 34 weeks at the time of surgery
- Weight less than 2500 grams at the time of surgery
- Abnormal renal function prior to cardiac surgery. Abnormal renal function is defined as a serum creatinine > 0.3mg/dL above baseline (lowest value in the preceding 3 months prior to surgery) compared to the level obtained immediately prior to cardiac surgery.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital Colorado
Aurora, Colorado, 80045
About this study
The purpose of this study is to identify if circulating platelet cyclic adenosine monophosphate (cAMP) levels can be used as a biomarker of milrinone efficacy in children following cardiac surgery or undergoing heart transplant.
Read the detailed description
Milrinone is a phosphodiesterase type III (PDE3) inhibitor with sites of action in cardiac and vascular smooth muscle. PDE3 hydrolyzes the critical second messenger cyclic adenosine monophosphate (cAMP), and PDE3 inhibition (PDE3i) results in a positive inotropic effect in the heart through an increase in cAMP. PDE3i causes relaxation of the vascular smooth muscle and induces vasodilation while concomitantly reducing myocardial oxygen consumption.
In adults, long term PDE3i results in malignant arrhythmias and an increased risk of sudden death, and is therefore not a recommended therapy in this population. However, in the pediatric Heart Failure (HF) population, long-term outpatient milrinone infusions are safely used as a palliative therapy or as a bridge to transplant without an increased risk of unexpected deaths, and results in fewer HF emergency department visits and admissions and improved New York Heart Association (NYHA)/Ross classification. In addition, short term PDE3i (i.e. milrinone) is successfully and routinely used in children presenting with decompensated HF following cardiac surgery. In children undergoing cardiac surgery with cardiopulmonary bypass there is a predictable fall in cardiac index 6 to 18 hours after cardiac surgery. This phenomenon is known as low cardiac output syndrome (LCOS) and is typified by tachycardia and poor perfusion resulting in end-organ dysfunction and risk for cardiac arrest. Milrinone is the only proven drug for prophylactic use in children following cardiac surgery for the prevention of LCOS.
While standard dosing of milrinone is routinely used in children, the actual dose-response relationship is unknown. Indeed, the investigators have noted significant variability in serum milrinone concentrations between patients despite weight based dosing strategies. This uncertainty in dosing is confounded by differences in patient age, size and ontologic maturation of the kidneys. Milrinone dose adjustments, therefore, vary widely among practitioners based on urine output, degree of systemic vasodilation and a change in serum creatinine. Additional uncertainty resides in the inability to easily identify the most appropriate milrinone dose to produce a biological effect (such as an increase in the critical secondary messenger, (cAMP) in the pediatric population.
Because milrinone is excreted as unchanged drug in the urine, kidney function is a critical factor in milrinone dosing. Recently published data demonstrate that 73% of milrinone levels in children with acute kidney injury (AKI) were outside the therapeutic range. Thus, children are particularly vulnerable to inappropriate milrinone dosing. Currently, AKI is diagnosed by an increase in serum creatinine (SCr). Unfortunately, the increase in SCr may not occur until 3 days after AKI occurs. Thus, in children treated with milrinone, undetected AKI would result in significant over-dosing. Since milrinone is also a potent vasodilator, excess milrinone dosing in AKI could lead to hypotension - and further exacerbation of AKI. Therefore, early detection of AKI is especially important in children receiving milrinone. Preliminary data demonstrate that supra therapeutic milrinone concentrations and urinary AKI biomarkers increase in advance of SCr in patients with AKI. In this grant, the investigators propose to determine if increases in Tissue inhibitor metalloproteinase and insulin like growth factor binding protein-7 (TIMP2xIGFBP7) (prior to an increase in SCr) will correlate with increased platelet cAMP and supra-therapeutic milrinone levels.
In the absence of the ability to identify the optimal dose, children are at risk for clinically relevant over or under-dosing with milrinone that can lead to hemodynamic compromise and end organ dysfunction. While clinical response to milrinone remains the most important factor in dose titration decisions, in order to fully optimize milrinone dosing and minimize drug-related toxicity, a biomarker representative of biologic milrinone effect is needed. The Investigators recently demonstrated that milrinone treatment results in increased myocardial cAMP levels and augmented phospholamban phosphorylation in children, but not in adults, with idiopathic dilated cardiomyopathy. In addition, preliminary data suggest that platelet cAMP levels correlate with tissue levels. The purpose of this study is to determine if platelet cAMP levels can serve as a circulating biomarker for end organ (cardiac) milrinone efficacy, and investigate whether changes in this biomarker correlate with clinical efficacy. Defining platelet cAMP levels in pediatric patients with heart disease would provide the basis for a personalized approach to milrinone dose titration and allow identification of those most likely to benefit from its use.
- Conditions
- Pediatrics, Heart Failure, Congenital Heart Disease, Therapeutics
- Keywords
- Milrinone
- Medical subject headings
- Heart Failure, Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Low cardiac output syndrome | Patients who experience low cardiac output syndrome | |
| No low cardiac output syndrome | Group that does not experience low cardiac output syndrome. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to the development of low cardiac output syndrome
Criteria for low cardiac output
Measured: Within 36 hours following cardiac surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2016 (estimated)
- Study startAug 2016
- Primary completion17 Aug 2017
- Study completion17 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for PediatricsStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Katja M Gist, DO, MSCS, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02728128
- Sponsor's protocol ID
- 15-2239
- Status last verified
- Mar 2020
- First submitted
- 8 Mar 2016
- Last updated
- 4 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
DiBianco R, Shabetai R, Kostuk W, Moran J, Schlant RC, Wright R. A comparison of oral milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure. N Engl J Med. 1989 Mar 16;320(11):677-83. doi: 10.1056/NEJM198903163201101.
PubMed 2646536Ewy GA. Inotropic infusions for chronic congestive heart failure: medical miracles or misguided medicinals? J Am Coll Cardiol. 1999 Feb;33(2):572-5. doi: 10.1016/s0735-1097(98)00596-8. No abstract available.
PubMed 9973041Hauptman PJ, Mikolajczak P, George A, Mohr CJ, Hoover R, Swindle J, Schnitzler MA. Chronic inotropic therapy in end-stage heart failure. Am Heart J. 2006 Dec;152(6):1096.e1-8. doi: 10.1016/j.ahj.2006.08.003.
PubMed 17161059Felker GM, O'Connor CM. Inotropic therapy for heart failure: an evidence-based approach. Am Heart J. 2001 Sep;142(3):393-401. doi: 10.1067/mhj.2001.117606.
PubMed 11526351Nony P, Boissel JP, Lievre M, Leizorovicz A, Haugh MC, Fareh S, de Breyne B. Evaluation of the effect of phosphodiesterase inhibitors on mortality in chronic heart failure patients. A meta-analysis. Eur J Clin Pharmacol. 1994;46(3):191-6. doi: 10.1007/BF00192547.
PubMed 8070498Packer M, Carver JR, Rodeheffer RJ, Ivanhoe RJ, DiBianco R, Zeldis SM, Hendrix GH, Bommer WJ, Elkayam U, Kukin ML, et al. Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. N Engl J Med. 1991 Nov 21;325(21):1468-75. doi: 10.1056/NEJM199111213252103.
PubMed 1944425Packer M, Medina N, Yushak M. Hemodynamic and clinical limitations of long-term inotropic therapy with amrinone in patients with severe chronic heart failure. Circulation. 1984 Dec;70(6):1038-47. doi: 10.1161/01.cir.70.6.1038.
PubMed 6388899Price JF, Towbin JA, Dreyer WJ, Moffett BS, Kertesz NJ, Clunie SK, Denfield SW. Outpatient continuous parenteral inotropic therapy as bridge to transplantation in children with advanced heart failure. J Card Fail. 2006 Mar;12(2):139-43. doi: 10.1016/j.cardfail.2005.11.001.
PubMed 16520263Birnbaum BF, Simpson KE, Boschert TA, Zheng J, Wallendorf MJ, Schechtman K, Canter CE. Intravenous home inotropic use is safe in pediatric patients awaiting transplantation. Circ Heart Fail. 2015 Jan;8(1):64-70. doi: 10.1161/CIRCHEARTFAILURE.114.001528. Epub 2014 Dec 3.
PubMed 25472966Berg AM, Snell L, Mahle WT. Home inotropic therapy in children. J Heart Lung Transplant. 2007 May;26(5):453-7. doi: 10.1016/j.healun.2007.02.004.
PubMed 17449413Hoffman TM, Wernovsky G, Atz AM, Bailey JM, Akbary A, Kocsis JF, Nelson DP, Chang AC, Kulik TJ, Spray TL, Wessel DL. Prophylactic intravenous use of milrinone after cardiac operation in pediatrics (PRIMACORP) study. Prophylactic Intravenous Use of Milrinone After Cardiac Operation in Pediatrics. Am Heart J. 2002 Jan;143(1):15-21. doi: 10.1067/mhj.2002.120305.
PubMed 11773907Gist KM, Mizuno T, Goldstein SL, Vinks A. Retrospective Evaluation of Milrinone Pharmacokinetics in Children With Kidney Injury. Ther Drug Monit. 2015 Dec;37(6):792-6. doi: 10.1097/FTD.0000000000000214.
PubMed 25860636
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Platelet and Tissue cAMP: Novel Biomarkers of Milrinone Efficacy in Children
- ClinicalTrials.gov ID
- NCT02728128
- Acronym / sponsor ID
- 15-2239
- Conditions
- Pediatrics, Heart Failure, Congenital Heart Disease, Therapeutics
- Keywords
- Milrinone
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- Aug 2016
- Primary completion
- 17 Aug 2017 (actual)
- Study completion
- 17 Aug 2017 (actual)
- First posted
- 5 Apr 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.
The purpose of this study is to identify if circulating platelet cyclic adenosine monophosphate (cAMP) levels can be used as a biomarker of milrinone efficacy in children following cardiac surgery or undergoing heart transplant.
Detailed description
Milrinone is a phosphodiesterase type III (PDE3) inhibitor with sites of action in cardiac and vascular smooth muscle. PDE3 hydrolyzes the critical second messenger cyclic adenosine monophosphate (cAMP), and PDE3 inhibition (PDE3i) results in a positive inotropic effect in the heart through an increase in cAMP. PDE3i causes relaxation of the vascular smooth muscle and induces vasodilation while concomitantly reducing myocardial oxygen consumption.
In adults, long term PDE3i results in malignant arrhythmias and an increased risk of sudden death, and is therefore not a recommended therapy in this population. However, in the pediatric Heart Failure (HF) population, long-term outpatient milrinone infusions are safely used as a palliative therapy or as a bridge to transplant without an increased risk of unexpected deaths, and results in fewer HF emergency department visits and admissions and improved New York Heart Association (NYHA)/Ross classification. In addition, short term PDE3i (i.e. milrinone) is successfully and routinely used in children presenting with decompensated HF following cardiac surgery. In children undergoing cardiac surgery with cardiopulmonary bypass there is a predictable fall in cardiac index 6 to 18 hours after cardiac surgery. This phenomenon is known as low cardiac output syndrome (LCOS) and is typified by tachycardia and poor perfusion resulting in end-organ dysfunction and risk for cardiac arrest. Milrinone is the only proven drug for prophylactic use in children following cardiac surgery for the prevention of LCOS.
While standard dosing of milrinone is routinely used in children, the actual dose-response relationship is unknown. Indeed, the investigators have noted significant variability in serum milrinone concentrations between patients despite weight based dosing strategies. This uncertainty in dosing is confounded by differences in patient age, size and ontologic maturation of the kidneys. Milrinone dose adjustments, therefore, vary widely among practitioners based on urine output, degree of systemic vasodilation and a change in serum creatinine. Additional uncertainty resides in the inability to easily identify the most appropriate milrinone dose to produce a biological effect (such as an increase in the critical secondary messenger, (cAMP) in the pediatric population.
Because milrinone is excreted as unchanged drug in the urine, kidney function is a critical factor in milrinone dosing. Recently published data demonstrate that 73% of milrinone levels in children with acute kidney injury (AKI) were outside the therapeutic range. Thus, children are particularly vulnerable to inappropriate milrinone dosing. Currently, AKI is diagnosed by an increase in serum creatinine (SCr). Unfortunately, the increase in SCr may not occur until 3 days after AKI occurs. Thus, in children treated with milrinone, undetected AKI would result in significant over-dosing. Since milrinone is also a potent vasodilator, excess milrinone dosing in AKI could lead to hypotension - and further exacerbation of AKI. Therefore, early detection of AKI is especially important in children receiving milrinone. Preliminary data demonstrate that supra therapeutic milrinone concentrations and urinary AKI biomarkers increase in advance of SCr in patients with AKI. In this grant, the investigators propose to determine if increases in Tissue inhibitor metalloproteinase and insulin like growth factor binding protein-7 (TIMP2xIGFBP7) (prior to an increase in SCr) will correlate with increased platelet cAMP and supra-therapeutic milrinone levels.
In the absence of the ability to identify the optimal dose, children are at risk for clinically relevant over or under-dosing with milrinone that can lead to hemodynamic compromise and end organ dysfunction. While clinical response to milrinone remains the most important factor in dose titration decisions, in order to fully optimize milrinone dosing and minimize drug-related toxicity, a biomarker representative of biologic milrinone effect is needed. The Investigators recently demonstrated that milrinone treatment results in increased myocardial cAMP levels and augmented phospholamban phosphorylation in children, but not in adults, with idiopathic dilated cardiomyopathy. In addition, preliminary data suggest that platelet cAMP levels correlate with tissue levels. The purpose of this study is to determine if platelet cAMP levels can serve as a circulating biomarker for end organ (cardiac) milrinone efficacy, and investigate whether changes in this biomarker correlate with clinical efficacy. Defining platelet cAMP levels in pediatric patients with heart disease would provide the basis for a personalized approach to milrinone dose titration and allow identification of those most likely to benefit from its use.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low cardiac output syndrome | – | –Patients who experience low cardiac output syndrome |
| No low cardiac output syndrome | – | –Group that does not experience low cardiac output syndrome. |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Children undergoing cardiac surgery with the use of cardiopulmonary bypass
Key inclusion criteria (4 listed)
- Children aged birth to 18 year of age
- Surgical complexity STAT score > 3
- Use of cardiopulmonary bypass for cardiac surgery
- Use of milrinone intra-operatively and post-operatively
Key exclusion criteria (4 listed)
- Patients on milrinone therapy prior to surgery
- Gestational age less than 34 weeks at the time of surgery
- Weight less than 2500 grams at the time of surgery
- Abnormal renal function prior to cardiac surgery. Abnormal renal function is defined as a serum creatinine > 0.3mg/dL above baseline (lowest value in the preceding 3 months prior to surgery) compared to the level obtained immediately prior to cardiac surgery.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Time to the development of low cardiac output syndrome
Time frame: Within 36 hours following cardiac surgery
Criteria for low cardiac output
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 4 Mar 2020.
- Background: PubMed 2646536DiBianco R, Shabetai R, Kostuk W, Moran J, Schlant RC, Wright R. A comparison of oral milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure. N Engl J Med. 1989 Mar 16;320(11):677-83. doi: 10.1056/NEJM198903163201101.
- Background: PubMed 9973041Ewy GA. Inotropic infusions for chronic congestive heart failure: medical miracles or misguided medicinals? J Am Coll Cardiol. 1999 Feb;33(2):572-5. doi: 10.1016/s0735-1097(98)00596-8. No abstract available.
- Background: PubMed 17161059Hauptman PJ, Mikolajczak P, George A, Mohr CJ, Hoover R, Swindle J, Schnitzler MA. Chronic inotropic therapy in end-stage heart failure. Am Heart J. 2006 Dec;152(6):1096.e1-8. doi: 10.1016/j.ahj.2006.08.003.
- Background: PubMed 11526351Felker GM, O'Connor CM. Inotropic therapy for heart failure: an evidence-based approach. Am Heart J. 2001 Sep;142(3):393-401. doi: 10.1067/mhj.2001.117606.
- Background: PubMed 8070498Nony P, Boissel JP, Lievre M, Leizorovicz A, Haugh MC, Fareh S, de Breyne B. Evaluation of the effect of phosphodiesterase inhibitors on mortality in chronic heart failure patients. A meta-analysis. Eur J Clin Pharmacol. 1994;46(3):191-6. doi: 10.1007/BF00192547.
- Background: PubMed 1944425Packer M, Carver JR, Rodeheffer RJ, Ivanhoe RJ, DiBianco R, Zeldis SM, Hendrix GH, Bommer WJ, Elkayam U, Kukin ML, et al. Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. N Engl J Med. 1991 Nov 21;325(21):1468-75. doi: 10.1056/NEJM199111213252103.
- Background: PubMed 6388899Packer M, Medina N, Yushak M. Hemodynamic and clinical limitations of long-term inotropic therapy with amrinone in patients with severe chronic heart failure. Circulation. 1984 Dec;70(6):1038-47. doi: 10.1161/01.cir.70.6.1038.
- Background: PubMed 16520263Price JF, Towbin JA, Dreyer WJ, Moffett BS, Kertesz NJ, Clunie SK, Denfield SW. Outpatient continuous parenteral inotropic therapy as bridge to transplantation in children with advanced heart failure. J Card Fail. 2006 Mar;12(2):139-43. doi: 10.1016/j.cardfail.2005.11.001.
- Background: PubMed 25472966Birnbaum BF, Simpson KE, Boschert TA, Zheng J, Wallendorf MJ, Schechtman K, Canter CE. Intravenous home inotropic use is safe in pediatric patients awaiting transplantation. Circ Heart Fail. 2015 Jan;8(1):64-70. doi: 10.1161/CIRCHEARTFAILURE.114.001528. Epub 2014 Dec 3.
- Background: PubMed 17449413Berg AM, Snell L, Mahle WT. Home inotropic therapy in children. J Heart Lung Transplant. 2007 May;26(5):453-7. doi: 10.1016/j.healun.2007.02.004.
- Background: PubMed 11773907Hoffman TM, Wernovsky G, Atz AM, Bailey JM, Akbary A, Kocsis JF, Nelson DP, Chang AC, Kulik TJ, Spray TL, Wessel DL. Prophylactic intravenous use of milrinone after cardiac operation in pediatrics (PRIMACORP) study. Prophylactic Intravenous Use of Milrinone After Cardiac Operation in Pediatrics. Am Heart J. 2002 Jan;143(1):15-21. doi: 10.1067/mhj.2002.120305.
- Background: PubMed 25860636Gist KM, Mizuno T, Goldstein SL, Vinks A. Retrospective Evaluation of Milrinone Pharmacokinetics in Children With Kidney Injury. Ther Drug Monit. 2015 Dec;37(6):792-6. doi: 10.1097/FTD.0000000000000214.
- Individual participant dataSharing planned: No
Related trials for Pediatrics
Not yet recruiting
Feasibility of a Robot-Guided Active Play Intervention for Children With Cerebral Palsy
Cerebral Palsy
RecruitingPhase 3
Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults
Seizures, Lennox Gastaut Syndrome
RecruitingPhase 4
A Study to Compare the Efficacy and Safety of Extended and Intermittent Infusion of Beta-lactams in Critically Ill Paediatric Patients
Infection, Sepsis
RecruitingObservational study
Psychological Benefits of a Normalized Camping Experience for Children With Cancer
Pediatric Cancer
Not yet recruitingObservational study
AI-assisted Tracheal Intubation in Children
Intubation
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.
Katja M Gist, DO, MSCS principal investigator
University of Colorado, Denver
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 Pediatrics and Heart Failure, run by University of Colorado, Denver at 1 site in United States.
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 4 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 4 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 United States. 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?
Time to the development of low cardiac output syndrome (time frame: Within 36 hours following cardiac surgery). 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 NCT02728128, which also lists 12 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 4 Mar 2020.