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Resuscitation With Plasma in Surgical and Trauma Patients With Septic Shock

Primary Purpose

Septic Shock

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Plasma
Balanced crystalloids
Sponsored by
The University of Texas Health Science Center, Houston
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Septic Shock

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The University of Texas Health Science Center at Houston

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

initial resuscitation with plasma

initial resuscitation with balanced crystalloids

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Glycocalyx Breakdown as Assessed by Syndecan-1 Levels
Glycocalyx Breakdown and Endothelial Leakage as Assessed by Soluble Thrombomodulin (sTM)
Endothelial Leakage as Assessed by Soluble FMS-like Tyrosine Kinase-1 (sFLT-1)
Endothelial Leakage and Inflammation as Assessed by Vascular Endothelial Growth Factor (VEGF)
Sympatho-adrenal Activation as Assessed by Norepinephrine (NE)
Sympatho-adrenal Activation as Assessed by Epinephrine (Epi)
Inflammation as Assessed by Soluble Receptor for Advanced Glycation Endproduct (sRAGE)
Inflammation as Assessed by High Mobility Group Protein-1 (HMGB-1)
Inflammation as Assessed by Interleukin-6 (IL-6)
Inflammation as Assessed by Interleukin-8 (IL-8)
Inflammation as Assessed by Interleukin-10 (IL-10)
Inflammation as Assessed by Interleukin-1α (IL-1α)
Inflammation as Assessed by Interleukin-1β (IL-1β)

Secondary Outcome Measures

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.
Time Until Lactate Normalization
Time on Vasopressors
Number of Days on Ventilator Support
Number of Intensive Care Unit (ICU)-Free Days
Number of Hospital Days
Mortality
Number of Participants With Acute Lung Injury
Number of Participants With Acute Kidney Injury

Full Information

First Posted
December 1, 2017
Last Updated
April 11, 2022
Sponsor
The University of Texas Health Science Center, Houston
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1. Study Identification

Unique Protocol Identification Number
NCT03366220
Brief Title
Resuscitation With Plasma in Surgical and Trauma Patients With Septic Shock
Official Title
Resuscitation With Plasma in Surgical and Trauma Patients With Septic Shock
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Terminated
Why Stopped
The study was halted early due to low patient accrual secondary to COVID-19 and significant heterogeneity in clinical manifestations of sepsis precluding enrollment.
Study Start Date
March 26, 2018 (Actual)
Primary Completion Date
September 17, 2019 (Actual)
Study Completion Date
October 16, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The University of Texas Health Science Center, Houston

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Septic Shock

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
InvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
initial resuscitation with plasma
Arm Type
Experimental
Arm Description
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.
Arm Title
initial resuscitation with balanced crystalloids
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Plasma
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Balanced crystalloids
Intervention Description
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.
Primary Outcome Measure Information:
Title
Glycocalyx Breakdown as Assessed by Syndecan-1 Levels
Time Frame
0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and at 24 hours
Title
Glycocalyx Breakdown and Endothelial Leakage as Assessed by Soluble Thrombomodulin (sTM)
Time Frame
0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours
Title
Endothelial Leakage as Assessed by Soluble FMS-like Tyrosine Kinase-1 (sFLT-1)
Time Frame
0, 2, end of initial bolus of fluid administration(about 3 hours), 12, and 24 hours
Title
Endothelial Leakage and Inflammation as Assessed by Vascular Endothelial Growth Factor (VEGF)
Time Frame
0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours
Title
Sympatho-adrenal Activation as Assessed by Norepinephrine (NE)
Time Frame
0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours
Title
Sympatho-adrenal Activation as Assessed by Epinephrine (Epi)
Time Frame
0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours
Title
Inflammation as Assessed by Soluble Receptor for Advanced Glycation Endproduct (sRAGE)
Time Frame
0, 2, end of initial bolus of fluid administration, 12, and 24 hours
Title
Inflammation as Assessed by High Mobility Group Protein-1 (HMGB-1)
Time Frame
0, 2, end of initial bolus of fluid administration, 12, and 24 hours
Title
Inflammation as Assessed by Interleukin-6 (IL-6)
Time Frame
0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours
Title
Inflammation as Assessed by Interleukin-8 (IL-8)
Time Frame
0, 2, end of initial bolus of fluid administration (about 3 hours) , 12, and 24 hours
Title
Inflammation as Assessed by Interleukin-10 (IL-10)
Time Frame
0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours
Title
Inflammation as Assessed by Interleukin-1α (IL-1α)
Time Frame
0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours
Title
Inflammation as Assessed by Interleukin-1β (IL-1β)
Time Frame
0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 24 hours
Secondary Outcome Measure Information:
Title
Total Volume of Fluid Required for Resuscitation After the Initial Bolus of Either Plasma or Crystalloids
Description
Data were not collected for 1 participant in the initial resuscitation with plasma arm.
Time Frame
First 24 hours after initiation of fluid resuscitation
Title
Time Until Lactate Normalization
Time Frame
First 24 hours after initiation of fluid resuscitation
Title
Time on Vasopressors
Time Frame
First 30 days after initiation of fluid resuscitation
Title
Number of Days on Ventilator Support
Time Frame
First 30 days after initiation of fluid resuscitation
Title
Number of Intensive Care Unit (ICU)-Free Days
Time Frame
First 30 days after initiation of fluid resuscitation
Title
Number of Hospital Days
Time Frame
From the time of initiation of fluid resuscitation to the time of hospital discharge (up to about 170 days)
Title
Mortality
Time Frame
First 30 days after initiation of fluid resuscitation
Title
Number of Participants With Acute Lung Injury
Time Frame
First 30 days after initiation of fluid resuscitation
Title
Number of Participants With Acute Kidney Injury
Time Frame
First 30 days after initiation of fluid resuscitation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shuyan Wei, MD
Organizational Affiliation
The University of Texas Health Science Center, Houston
Official's Role
Principal Investigator
Facility Information:
Facility Name
The University of Texas Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
30271882
Citation
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.
Results Reference
derived

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Resuscitation With Plasma in Surgical and Trauma Patients With Septic Shock

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