Clinical trial NCT06078436: Pulmonary Artery Catheterization and Carvedilol Early Initiation in Cardiogenic SHOCK Due to HFrEF
Official title: Pulmonary Artery Catheterization and Carvedilol Early Initiation in Cardiogenic SHOCK Caused by Heart Failure With Reduced Ejection Fraction
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Failure With Reduced Ejection Fraction
Cardiogenic Shock
Keywords: Cardiogenic shock
Heart failure with reduced ejection fraction (HFrEF)
Hemodynamic monitoring
Pulmonary artery catheter
Carvedilol
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
First posted: 2023-10-11
Enrollment: 160
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: From the time of diagnosing cardiogenic shock (CS) caused by HFrEF within 12 hours, random allocation will be conducted. If assigned to the hemodynamic monitoring group with pulmonary artery catheter (PAC), the catheter will be inserted and hemodynamic parameters will be monitored until recovery from CS. The non-monitoring group will receive CS treatment without inserting a PAC.
Primary purpose: TREATMENT

Brief summary: This study aims to compare the impact of hemodynamic monitoring using pulmonary artery catheter (PAC) on survival and inotropic agent reduction in patients with cardiogenic shock caused by heart failure with reduced ejection fraction (HFrEF). The investigators also intend to compare the difference in long-term survival rates among patients who have recovered from cardiogenic shock due to HFrEF, based on the timing of initiation of beta-blocker treatment.

Detailed description: Cardiogenic shock is one of the most common causes of shock patients admitted to the Cardiac Intensive Care Unit (CICU). Despite advances in treatment, the mortality rate of cardiogenic shock remains high, up to 50%, and improving survival is crucial through the use of inotropic agents, vasopressors, or mechanical circulatory support devices to improve hemodynamic parameters. Previous meta-analyses of retrospective studies have shown the usefulness of pulmonary artery catheter monitoring, especially in patients with cardiogenic shock due to heart failure. However, there is a lack of prospective studies regarding specific monitoring indicators and treatment goals. This study aims to compare the impact of hemodynamic monitoring through pulmonary artery catheter on survival and inotropic agent reduction in patients with cardiogenic shock caused by heart failure with reduced ejection fraction.

In the PAC non-monitoring group, various assessments such as physical examination, echocardiographic findings, serum lactate levels, chest x-ray, and laboratory test results are utilized. If there are signs of volume overload, diuretics or hemodialysis may be applied to achieve for volume reduction. The dosage of diuretics and the timing of hemodialysis are at the discretion of the attending physician. The target of a mean arterial pressure (MAP) is 65mmHg or higher. If the MAP falls below 65mmHg, increasing vasopressor or inotropes should be considered. If the MAP target is not achieved with medical therapy or if serum lactate levels increase by 3 mmol/L or more compared to the lowest value within 24 hours, mechanical circulatory support (MCS) is considered. The specific dosage of vasopressors/inotropes and the timing of MCS application are at the dscretion of the attending physician.

The PAC monitoring group, in addition to those used in the PAC non-monitoring group, treats patients using indicators measured by PAC. The targets include a right atrial pressure (RAP) or central venous pressure (CVP) of 8mmHg or lower and pulmonary capillary wedge pressure (PCWP) of 15mmHg or lower. Whan RAP or CVP exceeds 8mmHg, or PCWP exceeds 15mmHg, employing diuretics or hemodialysis should be considered for volume reduction. The dosage of diuretics and the timing of hemodialysis are at the discretion of the attending physician. The target of a mean arterial pressure (MAP) is 65mmHg or higher. If the MAP falls below 65mmHg, increasing vasopressor or inotropes should be considered. If the MAP target is not achieved with medical therapy or if serum lactate levels increase by 3 mmol/L or more compared to the lowest value within 24 hours, mechanical circulatory support (MCS) is considered. The specific dosage of vasopressors/inotropes and the timing of MCS application are at the dscretion of the attending physician.

Additionally, the beta-blocker Carvedilol is known to reduce mortality and readmission rates in heart failure patients based on large-scale clinical trials and is widely prescribed as a standard treatment. However, the evidence for the appropriate timing of Carvedilol initiation and objective indicators of hemodynamic stability beyond the point of discharge is currently insufficient, relying solely on the clinical judgment and experience of the treating physician. Through subgroup analysis, the investigators intend to compare the difference in long-term survival rates among patients who have recovered from cardiogenic shock due to heart failure with reduced ejection fraction, based on the timing of iniation of beta-blocker treatment. The early administration of Carvedilol is defined as initiating treatment within 24 to 48 hours after discontinuing vasopressor/inotropic agents or mechanical circulatory support in stable condition following cardiogenic shock. The conservative administration of Carvedilol is defined as initiating treatment at least 48 hours after discontinuing vasopressors/inotropic agents or mechanical circulatory support in stable condition following cardiogenic shock.

Also, lung B-line will be measure along with PAC measured hemodynamic parameters using lung ultrasound at eight regions of the thorax in patients with PAC monitoring. Number of B-line in a total and each region, positive region which is defined as having three or more number of B-line will be recorded. Acquired images will be adjudicated by two investigators who are blinded to the clinical information of the subject.

Eligibility criteria: Inclusion Criteria:

* Adults age 19 and above ( no age limit for elderly )
* Patients with cardiogenic shock requiring intensive care monitoring in ICU
* Patients eligible for oral medication administration
* Patients who have provided research participation consent through a written informed consent form

Exclusion Criteria:

* Unwilling or unable to obtain informed consent by the participant or substitute decision maker
* Patients with mechanical circulatory support at the time of screening
* Patients with acute coronary syndrome
* Patients with severe valvular heart disease requiring emergent percutaneous procedures or surgery
* Known hypersensitivity to beta-blockers
* Patients with a history of bronchospasm or asthma
* Patients with bradycardia or second or third-degree atrioventricular block
* Patients with sick sinus syndrome, including sinoatrial block
* Patients with untreated pheochromocytoma
* Patients currently undergoing de-sensitization therapy
* Patients who are currently pregnant, postpartum period within 30 days or breast-feeding

Primary outcomes:
measure: 30-day all-cause mortality
timeFrame: From date of randomization until the date of death from any cause, assessed up to 30 days
Secondary outcomes:
measure: All-cause mortality
timeFrame: From date of randomization until the date of death from any cause, assessed up to 3 months
measure: Cardiovascular mortality
timeFrame: From date of randomization until the date of death from any cause, assessed up to 3 months
measure: Timing of discontinuation of inotropic or vasopressor agents
timeFrame: From date of randomization until the date of discharge or assessed up to 90 days
measure: The rate of Carvedilol intake on the 3 months
timeFrame: 3 months from date of randomization
measure: The target-dose achievement rate of Carvedilol on the 3 months
timeFrame: 3 months from date of randomization
measure: 3-month follow-up echocardiography parameters
timeFrame: 3 months from date of randomization
measure: Complications related with pulmonary artery catheter
timeFrame: During hospitalization period, up to 30 days
measure: Hospitalization due to heart failure
timeFrame: 3 months from date of randomization
measure: The composite outcome of cardoivascular death and heart failure hospitalization
timeFrame: 3 months from date of randomization
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
affiliation: Asan Medical Center
name: Min-Seok Kim
role: STUDY_CHAIR
References: