Hypertonic Saline and Terlipressin for Sepsis-associated Hypotension (HYSATESS-p)

Hypertonic Saline and Terlipressin Linked To an Early Goal-Driven Protocol for Septic Shock or Sepsis-Associated Hypotension: A Pilot Trial (HYSATESS)

In hypotensive septic patients with controlled source, an hemodynamic management protocol including hypertonic saline (HS)and terlipressin improves MOD (Multiple Organ Dysfunction) Score by at least 3 points compared to the use of physiologic saline and norepinephrine.

The appropriate design for this trial would be factorial. For the time being, will consider de intervention as a whole unit for this pilot study. In the future an appropriately sized factorial multicentric study shall be necessary.

Other goals of the pilot study:

1. HS restores preload parameters adequately
2. HS associated with terlipressin normalizes blood pressure in septic shock
3. HS associated with terlipressin maintains plasma sodium levels 130-155mEq/L
4. There is an inverse relationship between plasma sodium and procalcitonin levels
5. HS increases plasma levels of vasopressin (AVP)
6. HS rises levels of cortisol but not of adrenocorticotropic hormone (ACTH)

Study Overview

• Status: Terminated
• Conditions: Septic Shock; Sepsis-associated Hypotension
• Intervention / Treatment: Drug: Hypertonic Saline and Terlipressin; Drug: Normal saline and norepinephrine

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Ciudad Real, Spain, 13005
    • Hospital General de Ciudad Real

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Criteria of SIRS: at least 2 of 4:

  • Temperature > 38 °c or < 36 ° C
  • More than 90 bpm heart rate
  • Respiratory rate more than 20rpm or PaCO2 less than 32 mm Hg or patient in mechanical ventilation
  • Less than 4000/ mm³ or more than 12000/mm³, or more than 10% leukocyte bands (immature)
• Septic source known demonstrated (or at least of high probability) and controlled (if it is controllable)
• Hematocrit 25% or higher and/or hemoglobin 8 g/dL or higher. If necessary, transfuse RBCs to meet this criteria
• MAP less than 70 mm Hg. Note there is no requirement for adequate preload evidence

Exclusion Criteria:

• Hypernatremia at base-line of 155 mEq/L or greater Hyponatremia at base-line less than 130mEq / L
• Prior endocrine disease affecting to the adrenal-pituitary axis.
• Intracranial Hypertension, brain tumor, seizures, head trauma
• Coronary Artery Disease active over the past year; or evidence of "myocardium at risk" by exercise stress test, pharmacological or positive gammagraphy last year without intervention
• Pregnancy
• Liver disease Child C, End-Stage-Renal-Disease
• Under the age of 18
• Patients with order "do not resuscitate" or with minimal chances to survive

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hypertonic Saline and Terlipressin	Drug: Hypertonic Saline and Terlipressin; Hypertonic saline 3% 7mL/Kg (with a maximum 500 mL)triggered by either Systolic Volume Variation or Pulse Pressure Variation more than 10%; Terlipressin infusion (dilution 1mg in 100mL) triggered by MAP below 70 mmHg for a goal MAP above 70 mmHg
Active Comparator: Normal Saline and norepinephrine	Drug: Normal saline and norepinephrine; Normal saline IV bolus 7mL/kg (with a maximum 500 mL)triggered by either Systolic Volume Variation or Pulse Pressure Variation above 10%; Norepinephrine drip (80 micrograms/mL) to keep MAP at least 70 mmHg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
MOD (Multiple Organ Dysfunction) Score	daily, as long as the patient stays in the ICU

Secondary Outcome Measures

Outcome Measure	Time Frame
Hypertonic Saline restores IV fluid response parameters (Pulse Pressure Variation or Systolic Volume Variation) adequately	First 48 hours
Hypertonic Saline associated with terlipressin maintains plasma sodium levels 130-155mEq/L	As long as Hypertonic saline plus terlipressin are in use and one week later
There is an inverse relationship between plasma sodium and plasma procalcitonin levels measured by a negative Pearson coefficient	As long as the patient stays in the ICU
Hypertonic Saline associated with terlipressin normalizes blood pressure in septic shock	First 48 hours
Hypertonic Saline boluses increases plasma levels of vasopressin (AVP)	First week in ICU
Hypertonic Saline use rises levels of cortisol but not of adrenocorticotropic hormone (ACTH)	First week in ICU

Collaborators and Investigators

• Sponsor: Hospital General de Ciudad Real
• Collaborators: University of Castilla-La Mancha
• Investigators: Principal Investigator: Javier Pascual Ramírez, HGCR; Study Chair: Luis COLLAR VIÑUELAS, MD, HGCR

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: January 4, 2011
• First Submitted That Met QC Criteria: January 5, 2011
• First Posted (Estimate): January 6, 2011

Study Record Updates

• Last Update Posted (Estimate): March 10, 2014
• Last Update Submitted That Met QC Criteria: March 7, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Sepsis; Toxemia; Shock, Septic; Hypotension; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Norepinephrine; Terlipressin
• Other Study ID Numbers: FISCAM AN-2010/28; 2010-024138-43 (EudraCT Number)