HYSATESS-p: Hypertonic Saline and Terlipressin for Sepsis-associated Hypotension

Sponsor

Hospital General de Ciudad Real (Other)

Overall Status

Terminated

CT.gov ID

NCT01271114

Collaborator

University of Castilla-La Mancha (Other)

Enrollment

Location

Arms

Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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:

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

Condition or Disease	Intervention/Treatment	Phase
Septic Shock Sepsis-associated Hypotension	Drug: Hypertonic Saline and Terlipressin Drug: Normal saline and norepinephrine	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

21 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jun 1, 2012

Actual Primary Completion Date :

Dec 1, 2013

Actual Study Completion Date :

Dec 1, 2013

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

MOD (Multiple Organ Dysfunction) Score [daily, as long as the patient stays in the ICU]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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