Resuscitation With Plasma in Surgical and Trauma Patients With Septic Shock

Phase 2

Terminated

Conditions: Septic Shock

Interventions: Drug: Balanced crystalloids
Drug: Plasma

Registration Number: NCT03366220

Lead Sponsor: The University of Texas Health Science Center, Houston

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 16

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
initial resuscitation with balanced crystalloids	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.
initial resuscitation with plasma	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.

Primary Outcome Measures

Name	Time	Method
Sympatho-adrenal Activation as Assessed by Norepinephrine (NE)	0, 2, end of initial bolus of fluid administration (about 3 hours), 12, and 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
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
Inflammation as Assessed by High Mobility Group Protein-1 (HMGB-1)	0, 2, end of initial bolus of fluid administration, 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 Interleukin-8 (IL-8)	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
Inflammation as Assessed by Interleukin-10 (IL-10)	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
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 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-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

Name	Time	Method
Number of Intensive Care Unit (ICU)-Free Days	First 30 days after initiation of fluid resuscitation
Time Until Lactate Normalization	First 24 hours after initiation of fluid resuscitation
Number of Days on Ventilator Support	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)
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
Total Volume of Fluid Required for Resuscitation After the Initial Bolus of Either Plasma or Crystalloids	First 24 hours after initiation of fluid resuscitation	Data were not collected for 1 participant in the initial resuscitation with plasma arm.
Time on Vasopressors	First 30 days after initiation of fluid resuscitation
Mortality	First 30 days after initiation of fluid resuscitation