CORTISHOCK-P: Trial of Corticosteroids in Inflammation-Enriched Heart Failure Cardiogenic Shock

Phase 2Not Yet RecruitingNCT07461961

Brigham and Women's Hospital30 enrolled

Overview

This pilot study investigates whether giving a short course of intravenous corticosteroids (methylprednisolone) alongside standard medical care can help patients recovering from heart failure-related cardiogenic shock. Heart failure-related cardiogenic shock happens when chronic heart dysfunction causes poor blood circulation and congestion throughout the body. Often, this condition triggers severe inflammation, making it harder for the heart and other organs to recover, even when temporary mechanical heart pumps are used to support blood flow. The study aims to see if reducing this inflammation with corticosteroids is safe and can help patients get better faster. Researchers will enroll 30 adult patients hospitalized with early-stage (SCAI Stage B or C) cardiogenic shock related to heart failure. To participate, patients must also show high levels of inflammation in their blood, specifically a high-sensitivity C-reactive protein (hsCRP) level of 20 mg/L or higher Participants will be randomly assigned by chance to one of two groups. One group will receive the standard of care alone. The other group will receive the standard of care plus a 7-day course of intravenous methylprednisolone. The main goal of the study is to measure the change in inflammation levels (hsCRP) over 7 days. Researchers will also monitor how well the patients' organs recover, track their need for blood pressure medications or mechanical heart pumps, and monitor for any side effects to ensure the treatment is safe

Heart failure-related cardiogenic shock (HF-CS) is currently the most common form of shock in contemporary cardiac intensive care units. While temporary mechanical circulatory support (tMCS) devices effectively restore cardiac output and stabilize central hemodynamics, patient outcomes remain poor, with mortality approaching 40-50%. A major barrier to recovery in these patients is systemic inflammation and immune dysregulation. This creates a state of "hemodynamic dissonance," where central hemodynamics are restored but peripheral circulatory failure and end-organ dysfunction persist. This condition is further exacerbated by critical illness-related corticosteroid insufficiency (CIRCI), present in up to 50% of cardiogenic shock patients, as well as the inflammatory response triggered by the extracorporeal circuits themselves. The CORTISHOCK-P trial is a prospective, randomized, open-label pilot study designed to test whether a short course of intravenous corticosteroids can effectively attenuate this systemic inflammatory storm. By specifically targeting patients with an inflammation-enriched phenotype (high-sensitivity C-reactive protein \[hsCRP\] ≥ 20 mg/L), this study introduces a biologically targeted pharmacological adjunct to complement tMCS and standard of care (SoC). The study will enroll 30 adult patients admitted to the intensive care units at Brigham and Women's Hospital and Massachusetts General Hospital. Eligible patients will have SCAI Stage B or C HF-CS and a left ventricular ejection fraction of \<40%. Following informed consent, participants will be randomized in a 1:1 ratio within 24 hours of admission to receive either standard of care alone or standard of care plus intravenous methylprednisolone. The pharmacological intervention consists of methylprednisolone administered at 80 mg IV once daily for 3 days, followed by a taper of 0.5 mg/kg/day for 4 additional days, for a total duration of 7 days. Methylprednisolone was selected for its potent anti-inflammatory properties and lower mineralocorticoid activity, minimizing fluid retention while maximizing inflammatory suppression. The primary objective is to evaluate the anti-inflammatory effects of the intervention, measured by the change in hsCRP concentrations from baseline to Day 7. Secondary objectives focus on clinical trajectories and resource utilization, including: Characterizing the impact of corticosteroids on circulatory support requirements, including vasoactive inotropic score (VIS) trends, as well as the escalation and weaning of tMCS devices. Determining the effects on organ dysfunction, specifically evaluating renal and hepatic dysfunction, as well as hemolysis indices. Assessing the overall feasibility, protocol adherence, and safety of administering corticosteroid therapy in this critically ill population. Safety will be continuously monitored, with specific attention given to adverse events such as hyperglycemia with ketoacidosis, new severe infections, gastrointestinal bleeding, and thromboembolic events. Clinical and laboratory assessments will be conducted daily from randomization through Day 7 or ICU discharge, with remote follow-up at 30 days post-discharge. Given the small sample size, statistical analyses will primarily focus on estimating effect sizes and precision to establish proof-of-concept and lay the groundwork for a definitive multicenter trial.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: Age ≥ 18 and ≤ 80 years. Hospitalized in the Intensive Care Unit (ICU). Cardiogenic shock defined by clinical and hemodynamic criteria. Hypotension defined by SBP \<90 mmHg for \>30 min, MAP \<60 mmHg for \>30 min, or requirement of vasopressors to maintain SBP ≥90 mmHg or MAP ≥60 mm Hg. Hypoperfusion defined by altered mental state, cold extremities, livedo reticularis, urine output \<30 mL/h, or lactate ≥2 mmol/L. If invasive hemodynamic monitoring is available, CI \<2.2 L/min/m2. SCAI stage B or stage C at the time of screening. For SCAI Stage B (Beginning Shock), clinical evidence of hemodynamic instability (including relative hypotension, a decline in SBP of ≥20-30 mmHg, or MAP \<20% from baseline, or tachycardia) without hypoperfusion (normal lactate). For SCAI Stage B, hypotension SBP \<90 mmHg or MAP \<60 mmHg or \> 30 mmHg drop from baseline, or tachycardia heart rate ≥100 bpm. For SCAI Stage C, requiring only one vasoactive/inotrope and/or IABP from admission with CS until randomization, AND Vasoactive-inotropic score (VIS) \<40. For SCAI Stage C, NONE of the following criteria of deterioration from admission until randomization: failure to respond to initial single vasopressor/inotrope drug and addition of a second drug, or failure to respond to IABP and need for new MCS device. For SCAI Stage C, use of vasoactive agents at the time of randomization must not show: low starting dose with escalation, intermediate starting dose without escalation or de-escalation, or high starting dose with de-escalation. For SCAI Stage C, worst lactate 2 - 5 mmol/L and increase ≥ 100% from baseline lactate ≥ 2mmol/L or worst lactate ≥5mmol/L. Documented history of chronic heart failure with reduced ejection fraction (LVEF \<40%). Etiology of cardiogenic shock must be congestive heart failure decompensation (HF-CS). hsCRP ≥20 mg/L, reflecting a pro-inflammatory state. Less than 48 hours since admission Exclusion Criteria: Cardiogenic shock caused by acute myocardial infarction (AMI-CS). Other special conditions causing cardiogenic shock, including post-cardiotomy CS, peripartum, adrenergic, valvular, restrictive, post-embolic, conduction or rhythm disorders, or related to cardiotropic drug intoxication. Circulatory shock of another cause, such as septic, hemorrhagic, or anaphylactic shock. Shock post-cardiac arrest. Onset of cardiogenic shock \>48 hours. SCAI stage A, D, or E at the time of enrollment. Severe hyperglycemia at baseline, defined as blood glucose ≥300 mg/dL despite insulin therapy. Ongoing uncontrollable infection, suspected concomitant sepsis, or mixed septic-cardiogenic shock. Ischemic hepatitis or ALT \>500 IU/L due to causes other than suspected hypoperfusion. Severe refractory acute kidney injury (AKI) at baseline, defined as new persistent anuria (urine output \<50 mL/day) or refractory AKI requiring new emergent renal replacement therapy. Known allergy to methylprednisolone or other steroid analogues. Cardiac transplant patient or on the transplant list. Patient planned for implantation of a durable LVAD. Moribund patients (SAPS2 \>90) or predicated mortality \>90% within 30 days. Signs of extremis, including lactate \>5 mmol/L, pH \<7.2, or refractory shock requiring escalation to \>3 vasopressors at screening. Pregnant woman, parturient, or breastfeeding mother. Adult person subject to a legal protection measure (guardianship, curatorship, safeguard of justice).

Outcomes

Primary Outcomes

Change in High-Sensitivity C-Reactive Protein (hsCRP) Concentration

The primary outcome is the change in hsCRP concentration, which serves as a biomarker-based measure of systemic inflammation to evaluate corticosteroid-mediated inflammatory modulation. To account for the pharmacokinetics of methylprednisolone, a 12-hour blanking period will be imposed; clinical outcomes occurring within the first 12 hours after treatment initiation will not be considered in the analysis

Time frame: Baseline, 24, 48, 72, and 96 hours, and at day 7 or ICU discharge

Secondary Outcomes

Change in Interleukin-6 (IL-6) Concentration

Serial measurements of key inflammatory biomarkers, including IL-6, will be performed to assess the mechanistic impact of corticosteroid therapy on inflammation.

Time frame: Baseline, 24, 48, 72, and 96 hours, and at day 7 or ICU discharge

Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and High-sensitivity troponin T (hs-TnT)Concentration

Serial measurements of NT-proBNP and hs-TnT will be performed to assess cardiac biomarker trajectories

Time frame: Baseline, 24, 48, 72, and 96 hours, and at day 7 or ICU discharge

Temporal Trends in Vasoactive Inotropic Score (VIS)

The VIS will be analyzed to assess hemodynamic recovery and the requirement for vasoactive support. The peak VIS, duration of high-dose vasoactive support, and sustained high-dose vasoactive requirement (VIS ≥40 or an increase of ≥10 points from baseline sustained for ≥6 hours) will be recorded

Time frame: Baseline, 24, 48, 72, and 96 hours, and at day 7 or ICU discharge

Escalation of Device Therapy

Escalation of device therapy is defined as progression from an intra-aortic balloon pump (IABP) to a microaxial flow pump or venoarterial extracorporeal membrane oxygenation (VA-ECMO). The type of device, timing of escalation, and duration of support will be recorded

Time frame: Through study completion, an average of 30 days

Successful Device Weaning

Successful device weaning is defined as the removal of temporary mechanical circulatory support (tMCS) without the recurrence of hemodynamic instability within 48 hours.

Time frame: Through study completion, an average of 30 days

Lactate Clearance

Lactate clearance is defined as the relative reduction in serum lactate levels compared to baseline. Persistent hyperlactatemia (lactate ≥3.0 mmol/L) or failure to achieve \>50% lactate clearance at 24 hours will be analyzed as markers of impaired metabolic recovery and tissue hypoperfusion

Time frame: 6, 12, 24, and 48 hours

Incidence of Adverse Events and Safety Outcomes

The safety of adjunctive methylprednisolone therapy will be monitored to identify adverse events associated with corticosteroid use and complications in critically ill patients. This includes monitoring for hyperglycemia resulting in ketoacidosis, serious infections, gastrointestinal complications, and thromboembolic events

Time frame: through study completion, an average of 30 days

CORTISHOCK-P: Trial of Corticosteroids in Inflammation-Enriched Heart Failure Cardiogenic Shock

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts