Heart FailureCIPHERNCT04323371
Cardiogenic Shock Integrated PHenotyping for Event Reduction
An observational study of Heart Failure, run by Niguarda Hospital at 1 site in Italy.
Trial summary
The purpose of this study is to better understand the time course of different biological mechanisms involved in acute decompensated heart failure complicated by cardiogenic shock throughout the evaluation of changes and the relationship among markers of inflammation (IL-6) and markers of increased endothelial… Read more about this study
- Who is it for?
- Ages 18 to 74 years
- Conditions the study is for
- Heart Failure
- What is being tested?
- ELISA
- How many people
- 26 participants
- Where
- 1 siteItaly
- Study dates
- 30 Jun 2020to 1 Mar 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 to 74 years
- All sexes
- Adult, Older adult
Study population: Patients with acute decompensated heart failure, complicated by cardiogenic shock
Who may be able to join
- Age ≥ 18 and < 75, men and women;
- 1) Systolic blood pressure (SBP) < 90mmHg or mean arterial pressure (MAP) < 60 mmHg, after an appropriate fluid challenge if there is no sign of overt fluid overload; OR 2) need of vasoactive agents to maintain SBP > 90 mmHg or MAP > 60 mmHg.
- Reduced ejection fraction (left ventricle systolic function ≤35%).
- Moreover, eligible patients have to fit at least ONE of the following criteria/items of overt hypoperfusion: altered state of consciousness; sweaty and cold skin; mixed venous oxygen saturation < 60%; arterial lactates > 2 mmol/L; oliguria < 0.5 ml/Kg/h for at least 6 hours.
- Eligible patients shouldn't have contraindications to heart replacement therapy (HRT).
Who cannot join
- The participant will not be enrolled if ANY of the following criteria will be detected:
- Cardiogenic shock symptoms beyond 6 hours.
- Septic shock with evident septic focus.
- Cardiogenic shock due to acute myocardial infarction.
- Cardiogenic shock due to acute myocarditis.
- Cardiogenic shock due to pulmonary thromboembolism.
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- Reiterating major arrhythmias: VT or VF or AF, with ventricular rate > 160 bpm.
- Severe aortic valve disease.
- Obstructive hypertrophic cardiomyopathy or constrictive pericarditis or severe heart failure due to congenital heart disease
- Severe peripheral vascular disease that contraindicates mechanical support insertion.
- Cardiogenic shock secondary to either cardiac or non-cardiac surgery.
- Comorbidities with ominous prognosis (life expectancy < 1 year).
- Estimated glomerular filtration rate severely impaired before enrolment (eGFR<30 ml/min/1.73 m2) or severe chronic obstructive pulmonary disease (COPD) or liver cirrhosis.
- Pregnant, lactating or subjects planning pregnancy during the course of the trial.
- Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
Milan, 20162
Nuccia Morici, MD, +39026444 ext. 2643, nuccia.morici@ospedaleniguarda.it
Alice Sacco, MD, +39026444 ext. 2576, alice.sacco@ospedaleniguarda.it
About this study
The purpose of this study is to better understand the time course of different biological mechanisms involved in acute decompensated heart failure complicated by cardiogenic shock throughout the evaluation of changes and the relationship among markers of inflammation (IL-6) and markers of increased endothelial permeability (Ang-2) or endothelial glycocalyx perturbation (Syndecan-1 and HS) and throughout a targeted metabolomic approach.
Read the detailed description
Cardiogenic shock (CS) is a heterogenous syndrome with in-hospital mortality up to 60%, that, unfortunately, has remained stagnant over the time, despite observed improvements with pharmacological and non-pharmacological approach, even though only in terms of haemodynamic stabilization.
While very early mortality in CS is largely related to sudden and severe circulation failure, subsequent death is strongly influenced by activation of neurohumoral and inflammatory response leading to multiorgan failure. Previous studies on CS have almost exclusively been focused on CS following an acute coronary syndrome (ACS). Patients with acutely decompensated heart failure (ADHF) represent a different pathophysiologic phenotype compared with acute coronary syndrome (ACS) patients, which may lead to a differential response to device therapy.
In the face of complex biological phenomena guidelines are incapable of distinguishing the underlying pathophysiological mechanisms and give us input to standardize, whereas there is an unmet need for a personalized medicine.
The evaluation of changes and the relationship among markers of inflammation (IL-6) and markers of increased endothelial permeability (Ang-2) or endothelial glycocalyx perturbation (Syndecan-1 and HS) and an exploratory analysis throughout targeted metabolomics may help us to better understand the time course of different biological mechanisms involved in CS.
- Conditions
- Heart Failure
- Being tested
- ELISA
- Keywords
- heart failure, cardiogenic shock, endothelial glycocalyx, Angiopoietin (Ang)-2, Metabolomics
- Medical subject headings
- Heart Failure, Shock, Cardiogenic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ELISADiagnostic test
Blood and derived fluids will be collected from 26 ADHF CS patients admitted to intensive care at Niguarda Hospital and locally stored.Stocked samples will be shipped to the Central Laboratories at Milano Uni and MilaIFC-CNR for the metabolomic and biomarkers analysis,respectively.To evaluate interleukin-6 (marker of systemic inflammation),angiopoietin-2 (marker of endothelial permeability), syndecan-1 and heparan sulfate (markers of endothelial glycocalyx),2 aliquotes of serum samples will be used by IFC CNR.The biomarkers will be assessed through ELISA analytical techniques, based on the interactions inside a microplate between a primary pre-coated antibody and the specific protein contained in serum samples.A secondary antibody, link to a horseradish peroxidase (HRP) detection system, is able to recognize and bind the antigen, and to produce a colorimetric reaction after the addition of enzyme substrate which is proportional to the amount of the target protein bound
| Study group | Role | What they receive |
|---|---|---|
| Acute decompensated heart failure | patients admitted with Acute decompensated heart failure Complicated by cardiogenic shock Receives: Diagnostic Test: ELISA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Value of Interleukin 6 (IL-6)
Markers of inflammation. Unit of measure: pg/mL.
Measured: 3 years
Value of Angiopoietin 2 (Ang-2)
Markers of endothelial permeability. Unit of measure: ng/mL.
Measured: 3 years
Value of Syndecan-1
Endothelial glycocalyx perturbation. Unit of measure: ng/mL.
Measured: 3 years
Value of Heparan sulfate (HS)
Endothelial glycocalyx perturbation: Unit of measure: ug/mL.
Measured: 3 years
Metabolomics profiling
Exporatory assessment of targeted metabolomics through the quantification of almost 180 molecules, including acylcarnitines, amino acids and biogenic amines, hexoside, sphingolipids and glycerophospholipids.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2020
- Study start30 Jun 2020
- Primary completion1 Mar 2024
- Study completion1 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies 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
- 26 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Niguarda Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04323371
- Sponsor's protocol ID
- 43-12022020
- Acronym
- CIPHER
- Status last verified
- Apr 2026
- First submitted
- 11 Mar 2020
- Last updated
- 16 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiogenic Shock Integrated PHenotyping for Event Reduction
- ClinicalTrials.gov ID
- NCT04323371
- Acronym / sponsor ID
- CIPHER / 43-12022020
- Conditions
- Heart Failure
- Keywords
- heart failure, cardiogenic shock, endothelial glycocalyx, Angiopoietin (Ang)-2, Metabolomics
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 26 participants (estimated)
- Lead sponsor
- Niguarda HospitalUniversity, hospital or other
- Study start
- 30 Jun 2020 (actual)
- Primary completion
- 1 Mar 2024 (actual)
- Study completion
- 1 Mar 2028 (estimated)
- First posted
- 26 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.
The purpose of this study is to better understand the time course of different biological mechanisms involved in acute decompensated heart failure complicated by cardiogenic shock throughout the evaluation of changes and the relationship among markers of inflammation (IL-6) and markers of increased endothelial permeability (Ang-2) or endothelial glycocalyx perturbation (Syndecan-1 and HS) and throughout a targeted metabolomic approach.
Detailed description
Cardiogenic shock (CS) is a heterogenous syndrome with in-hospital mortality up to 60%, that, unfortunately, has remained stagnant over the time, despite observed improvements with pharmacological and non-pharmacological approach, even though only in terms of haemodynamic stabilization.
While very early mortality in CS is largely related to sudden and severe circulation failure, subsequent death is strongly influenced by activation of neurohumoral and inflammatory response leading to multiorgan failure. Previous studies on CS have almost exclusively been focused on CS following an acute coronary syndrome (ACS). Patients with acutely decompensated heart failure (ADHF) represent a different pathophysiologic phenotype compared with acute coronary syndrome (ACS) patients, which may lead to a differential response to device therapy.
In the face of complex biological phenomena guidelines are incapable of distinguishing the underlying pathophysiological mechanisms and give us input to standardize, whereas there is an unmet need for a personalized medicine.
The evaluation of changes and the relationship among markers of inflammation (IL-6) and markers of increased endothelial permeability (Ang-2) or endothelial glycocalyx perturbation (Syndecan-1 and HS) and an exploratory analysis throughout targeted metabolomics may help us to better understand the time course of different biological mechanisms involved in CS.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Acute decompensated heart failure | – | Diagnostic Test: ELISApatients admitted with Acute decompensated heart failure Complicated by cardiogenic shock |
Who may qualify
- Ages
- 18 to 74 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Patients with acute decompensated heart failure, complicated by cardiogenic shock
Key inclusion criteria (5 listed)
- Age ≥ 18 and < 75, men and women;
- 1) Systolic blood pressure (SBP) < 90mmHg or mean arterial pressure (MAP) < 60 mmHg, after an appropriate fluid challenge if there is no sign of overt fluid overload; OR 2) need of vasoactive agents to maintain SBP > 90 mmHg or MAP > 60 mmHg.
- Reduced ejection fraction (left ventricle systolic function ≤35%).
- Moreover, eligible patients have to fit at least ONE of the following criteria/items of overt hypoperfusion: altered state of consciousness; sweaty and cold skin; mixed venous oxygen saturation < 60%; arterial lactates > 2 mmol/L; oliguria < 0.5 ml/Kg/h for at least 6 hours.
- Eligible patients shouldn't have contraindications to heart replacement therapy (HRT).
Key exclusion criteria (15 listed)
- Cardiogenic shock symptoms beyond 6 hours.
- Septic shock with evident septic focus.
- Cardiogenic shock due to acute myocardial infarction.
- Cardiogenic shock due to acute myocarditis.
- Cardiogenic shock due to pulmonary thromboembolism.
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 |
|---|---|---|
| ELISABlood and derived fluids will be collected from 26 ADHF CS patients admitted to intensive care at Niguarda Hospital and locally stored.Stocked samples will be shipped to the Central Laboratories at Milano Uni and MilaIFC-CNR for the metabolomic and biomarkers analysis,respectively.To evaluate interleukin-6 (marker of systemic inflammation),angiopoietin-2 (marker of endothelial permeability), syndecan-1 and heparan sulfate (markers of endothelial glycocalyx),2 aliquotes of serum samples will be used by IFC CNR.The biomarkers will be assessed through ELISA analytical techniques, based on the interactions inside a microplate between a primary pre-coated antibody and the specific protein contained in serum samples.A secondary antibody, link to a horseradish peroxidase (HRP) detection system, is able to recognize and bind the antigen, and to produce a colorimetric reaction after the addition of enzyme substrate which is proportional to the amount of the target protein bound | Diagnostic test | Acute decompensated heart failure |
Primary outcome
Value of Interleukin 6 (IL-6)
Time frame: 3 years
Markers of inflammation. Unit of measure: pg/mL.
Value of Angiopoietin 2 (Ang-2)
Time frame: 3 years
Markers of endothelial permeability. Unit of measure: ng/mL.
Value of Syndecan-1
Time frame: 3 years
Endothelial glycocalyx perturbation. Unit of measure: ng/mL.
Value of Heparan sulfate (HS)
Time frame: 3 years
Endothelial glycocalyx perturbation: Unit of measure: ug/mL.
Metabolomics profiling
Time frame: 3 years
Exporatory assessment of targeted metabolomics through the quantification of almost 180 molecules, including acylcarnitines, amino acids and biogenic amines, hexoside, sphingolipids and glycerophospholipids.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2026.
- Individual participant dataSharing planned: Undecided
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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.
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 Heart Failure, run by Niguarda Hospital at 1 site in Italy.
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 15 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: looking for participants now, as of the sponsor's last update on 16 Apr 2026. 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 Italy. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nuccia Morici, MD (+39026444 ext. 2643, nuccia.morici@ospedaleniguarda.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Value of Interleukin 6 (IL-6) (time frame: 3 years). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Apr 2026.