Pulmonary Artery Catheterization and Carvedilol Early Initiation in Cardiogenic SHOCK Due to HFrEF

Heart Failure With Reduced Ejection Fraction Clinical Trial

— PACE-SHOCK  

Official title:

Pulmonary Artery Catheterization and Carvedilol Early Initiation in Cardiogenic SHOCK Caused by Heart Failure With Reduced Ejection Fraction

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06078436
• Other study ID #: AMC_2023_0794
• Status: Recruiting
• Phase: N/A
• Start date: January 2024
• Est. completion date: March 2028

Study information

• Verified date: January 2024
• Source: Asan Medical Center
• Contact: Min-Seok Kim, PhD
• Phone: 82-2-3010-3948
• Email: msk[@]amc.seoul.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: March 2028
• Est. primary completion date: September 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiogenic Shock
• Heart Failure
• Heart Failure With Reduced Ejection Fraction
• Shock
• Shock, Cardiogenic

Intervention

Device:
• Pulmonary artery catheter
Pulmonary artery catheter monitoring or not

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Min-Seok Kim

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	30-day all-cause mortality	All-cause mortality	From date of randomization until the date of death from any cause, assessed up to 30 days
Secondary	All-cause mortality	All-cause of death	From date of randomization until the date of death from any cause, assessed up to 3 months
Secondary	Cardiovascular mortality	Cardiovascular death	From date of randomization until the date of death from any cause, assessed up to 3 months
Secondary	Timing of discontinuation of inotropic or vasopressor agents	Days from randomization to discontinuation of inotropes/vasopressor	From date of randomization until the date of discharge or assessed up to 90 days
Secondary	The rate of Carvedilol intake on the 3 months	The rate of Carvedilol intake	3 months from date of randomization
Secondary	The target-dose achievement rate of Carvedilol on the 3 months	Target dose : 50mg/day	3 months from date of randomization
Secondary	3-month follow-up echocardiography parameters	LVEF(left ventricular ejection fraction)	3 months from date of randomization
Secondary	Complications related with pulmonary artery catheter	Any complications related with pulmonary artery catheter	During hospitalization period, up to 30 days
Secondary	Hospitalization due to heart failure	Unplanned hospitalization due to heart failure	3 months from date of randomization
Secondary	The composite outcome of cardoivascular death and heart failure hospitalization	The composite outcome of cardiovascular death and hospitalization due to heart failure	3 months from date of randomization