Hypertonic Saline and Terlipressin for Sepsis-associated Hypotension

Septic Shock Clinical Trial

— HYSATESS-p  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01271114
• Other study ID #: FISCAM AN-2010/28
• Secondary ID: 2010-024138-43
• Status: Terminated
• Phase: Phase 3
• First received: January 4, 2011
• Last updated: March 7, 2014
• Start date: June 2012
• Est. completion date: December 2013

Study information

• Verified date: March 2014
• Source: Hospital General de Ciudad Real
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial Summary

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)

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 21
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypotension
• Sepsis
• Sepsis-associated Hypotension
• Septic Shock
• Shock, Septic

Intervention

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
• 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

Locations

Country	Name	City	State
Spain	Hospital General de Ciudad Real	Ciudad Real

Sponsors (2)

Lead Sponsor	Collaborator
Hospital General de Ciudad Real	University of Castilla-La Mancha

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MOD (Multiple Organ Dysfunction) Score		daily, as long as the patient stays in the ICU	Yes
Secondary	Hypertonic Saline restores IV fluid response parameters (Pulse Pressure Variation or Systolic Volume Variation) adequately		First 48 hours	No
Secondary	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	Yes
Secondary	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	No
Secondary	Hypertonic Saline associated with terlipressin normalizes blood pressure in septic shock		First 48 hours	No
Secondary	Hypertonic Saline boluses increases plasma levels of vasopressin (AVP)		First week in ICU	No
Secondary	Hypertonic Saline use rises levels of cortisol but not of adrenocorticotropic hormone (ACTH)		First week in ICU	No