Resuscitation With Plasma in Surgical and Trauma Patients With Septic Shock

There is a knowledge gap regarding the optimal initial fluid to achieve effective resuscitation and improved outcomes in septic shock. The purpose of this study is to compare initial resuscitation with plasma to initial resuscitation with balanced crystalloids.

Study Overview

• Status: Terminated
• Conditions: Septic Shock
• Intervention / Treatment: Drug: Plasma; Drug: Balanced crystalloids

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients meeting the following criteria will be enrolled: Have a Sepsis Screening Score (SSS) ≥ 4 with a suspected source of infection (Table 1); and Written informed consent obtained
• Patients meeting any of the following criteria will be randomized: Hypotension with MAP < 65 mmHg; Lactic acid > 4 mmol/L; Altered mental status; and Decreased urine output of < 0.5 mL/kg in the past hour.

Exclusion Criteria:

• Pregnancy
• Prisoners
• Traumatic brain injury
• Evidence of ongoing hemorrhage, history of congenital bleeding disorders, therapeutic anticoagulation
• History of myocardial infarction or congestive heart failure
• History of acute cerebral vascular event
• Major burns (>20% total body surface area)
• History of adverse reactions to blood product transfusion
• Contraindications to blood transfusions (eg. Jehovah's Witness)
• Contraindications to central venous line and arterial line placement
• On intermittent hemodialysis
• Do-Not-Resuscitate or Comfort Care status
• Participation in another interventional study
• Pending transfer to another unit within the hospital that is not STICU or SIMU

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: initial resuscitation with plasma; Initial resuscitation with plasma will be 10 mL/kg (700 mL in a typical 70 kg adult). Traditional doses of plasma, when used to correct coagulopathy range from 10-15 mL/kg.23 The plasma will be administered at a rate of 2-3 mL/kg/hr (140-210 mL/hr in a typical 70 kg adult). A research physician will be at bedside to follow patient resuscitation. Plasma administration may be terminated before the entire dose is administered if patients show clinical improvement. After the initial dose of plasma has been given, subsequent resuscitation will follow usual care using balanced crystalloids.	Drug: Plasma; Initial resuscitation with plasma will be 10 mL/kg (700 mL in a typical 70 kg adult). Traditional doses of plasma, when used to correct coagulopathy range from 10-15 mL/kg.23 The plasma will be administered at a rate of 2-3 mL/kg/hr (140-210 mL/hr in a typical 70 kg adult). A research physician will be at bedside to follow patient resuscitation. Plasma administration may be terminated before the entire dose is administered if patients show clinical improvement. After the initial dose of plasma has been given, subsequent resuscitation will follow usual care using balanced crystalloids.
Active Comparator: initial resuscitation with balanced crystalloids; Usual care using balanced crystalloids (Iso-Lyte or Plasma-Lyte) only will follow Surviving Sepsis Campaign guidelines. Controls will receive 30 mL/kg (2100 mL in a typical 70 kg adult) of crystalloids within the first 3 hours. Subsequent resuscitation with balanced crystalloids will be titrated to the endpoints of resuscitation.	Drug: Balanced crystalloids; Usual care using balanced crystalloids (Iso-Lyte or Plasma-Lyte) only will follow Surviving Sepsis Campaign guidelines. Controls will receive 30 mL/kg (2100 mL in a typical 70 kg adult) of crystalloids within the first 3 hours. Subsequent resuscitation with balanced crystalloids will be titrated to the endpoints of resuscitation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Glycocalyx Breakdown as Assessed by Syndecan-1 Levels	0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and at 24 hours
Glycocalyx Breakdown and Endothelial Leakage as Assessed by Soluble Thrombomodulin (sTM)	0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours
Endothelial Leakage as Assessed by Soluble FMS-like Tyrosine Kinase-1 (sFLT-1)	0, 2, end of initial bolus of fluid administration(about 3 hours), 12, and 24 hours
Endothelial Leakage and Inflammation as Assessed by Vascular Endothelial Growth Factor (VEGF)	0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours
Sympatho-adrenal Activation as Assessed by Norepinephrine (NE)	0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours
Sympatho-adrenal Activation as Assessed by Epinephrine (Epi)	0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours
Inflammation as Assessed by Soluble Receptor for Advanced Glycation Endproduct (sRAGE)	0, 2, end of initial bolus of fluid administration, 12, and 24 hours
Inflammation as Assessed by High Mobility Group Protein-1 (HMGB-1)	0, 2, end of initial bolus of fluid administration, 12, and 24 hours
Inflammation as Assessed by Interleukin-6 (IL-6)	0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours
Inflammation as Assessed by Interleukin-8 (IL-8)	0, 2, end of initial bolus of fluid administration (about 3 hours) , 12, and 24 hours
Inflammation as Assessed by Interleukin-10 (IL-10)	0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours
Inflammation as Assessed by Interleukin-1α (IL-1α)	0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours
Inflammation as Assessed by Interleukin-1β (IL-1β)	0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Volume of Fluid Required for Resuscitation After the Initial Bolus of Either Plasma or Crystalloids	Data were not collected for 1 participant in the initial resuscitation with plasma arm.	First 24 hours after initiation of fluid resuscitation
Time Until Lactate Normalization		First 24 hours after initiation of fluid resuscitation
Time on Vasopressors		First 30 days after initiation of fluid resuscitation
Number of Days on Ventilator Support		First 30 days after initiation of fluid resuscitation
Number of Intensive Care Unit (ICU)-Free Days		First 30 days after initiation of fluid resuscitation
Number of Hospital Days		From the time of initiation of fluid resuscitation to the time of hospital discharge (up to about 170 days)
Mortality		First 30 days after initiation of fluid resuscitation
Number of Participants With Acute Lung Injury		First 30 days after initiation of fluid resuscitation
Number of Participants With Acute Kidney Injury		First 30 days after initiation of fluid resuscitation

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Investigators: Principal Investigator: Shuyan Wei, MD, The University of Texas Health Science Center, Houston

Publications and helpful links

General Publications

• Wei S, Kao LS, Wang HE, Chang R, Podbielski J, Holcomb JB, Wade CE. Protocol for a pilot randomized controlled trial comparing plasma with balanced crystalloid resuscitation in surgical and trauma patients with septic shock. Trauma Surg Acute Care Open. 2018 Sep 23;3(1):e000220. doi: 10.1136/tsaco-2018-000220. eCollection 2018.

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2018
• Primary Completion (Actual): September 17, 2019
• Study Completion (Actual): October 16, 2019

Study Registration Dates

• First Submitted: December 1, 2017
• First Submitted That Met QC Criteria: December 1, 2017
• First Posted (Actual): December 8, 2017

Study Record Updates

• Last Update Posted (Actual): April 13, 2022
• Last Update Submitted That Met QC Criteria: April 11, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock
• Other Study ID Numbers: HSC-MS-17-0714

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No