Resuscitation With Plasma in Surgical and Trauma Patients With Septic Shock

NCT03366220 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: HSC-MS-17-0714
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Septic Shock

Outcome Measures

Primary Outcomes (13)

• 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 Outcomes (9)

• Total Volume of Fluid Required for Resuscitation After the Initial Bolus of Either Plasma or Crystalloids

  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

Study Arms (2)

initial resuscitation with plasma

EXPERIMENTAL

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 balanced crystalloids

ACTIVE COMPARATOR

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

Interventions

Plasma DRUG

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.

initial resuscitation with plasma

Balanced crystalloids DRUG

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.

initial resuscitation with balanced crystalloids

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead

Study Sites (1)

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 30271882 DERIVED

MeSH Terms

Conditions

Shock, Septic

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Results Point of Contact

• Title: Dr. Lillian S Kao
• Organization: The University of Texas Health Science Center at Houston

Lillian.S.Kao@uth.tmc.edu

(713) 500-6280

Study Officials

• Shuyan Wei, MD

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 1, 2017
• First Posted: December 8, 2017
• Study Start: March 26, 2018
• Primary Completion: September 17, 2019
• Study Completion: October 16, 2019
• Last Updated: April 13, 2022
• Results First Posted: April 13, 2022

Record last verified: 2022-04

Locations

US (1)