# Study of Treatment's Echocardiographic Mechanisms (CLOVERS-STEM)

> **NIH NIH R01** · IHC HEALTH SERVICES, INC. · 2021 · $498,997

## Abstract

Project Summary/Abstract
Sepsis results when the host response to infection—comprising both immune and stress responses—leads to
organ dysfunction, centrally cardiovascular dysfunction. The resulting sepsis-associated hypotension is lethal;
how best to treat it is currently unknown. The two main treatments—intravenous fluid and catecholamine
vasopressor infusions—both have toxicities, including direct effects on the heart, thus contributing to what is
often termed septic cardiomyopathy.
A large NIH/NHLBI-funded clinical trial, Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis
(CLOVERS), randomizes patients to competing strategies for treating sepsis-associated hypotension: liberal
fluids (≥5L fluids before vasopressors) or early vasopressors (immediate vasopressors without additional
fluids). CLOVERS represents an ideal laboratory for understanding the effects of management strategies on
the evolution of septic cardiomyopathy, the relative contributions of right ventricular (RV) and left ventricular
(LV) impairment to outcomes from septic cardiomyopathy, and the implications of baseline echocardiographic
findings for the effect of treatments in certain groups of people. The Study of Treatment’s Echocardiographic
Mechanisms (CLOVERS-STEM) is a prospective observational ancillary study within CLOVERS. Study
subjects (N=210) will undergo speckle-tracked echocardiograms at enrollment and 24 hours later. Three
integrated aims employ robust echocardiographic measures to assess the evolution of septic cardiomyopathy
and differential susceptibility to treatment.
Aim 1 assesses whether the early vasopressor treatment leads to LV impairment at 24 hours, as measured by
global longitudinal strain. Aim 2 assesses whether the early vasopressor treatment leads to RV impairment, as
measured by the ratio of RV to LV end-diastolic areas and RV free wall longitudinal strain. These two aims will
also explore the contributions of LV and RV impairment to clinical endpoints. Aim 3 uses a validated
continuous surrogate outcome—the change in multiple organ dysfunction on day 3—to explore possible
heterogeneity of treatment effect based on the baseline echocardiographic results. This project innovates in
multiple respects to dramatically advance our understanding of a major cause of global morbidity and mortality.

## Key facts

- **NIH application ID:** 10179455
- **Project number:** 5R01HL144624-03
- **Recipient organization:** IHC HEALTH SERVICES, INC.
- **Principal Investigator:** Samuel Morris Brown
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $498,997
- **Award type:** 5
- **Project period:** 2019-06-10 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10179455

## Citation

> US National Institutes of Health, RePORTER application 10179455, Study of Treatment's Echocardiographic Mechanisms (CLOVERS-STEM) (5R01HL144624-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10179455. Licensed CC0.

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