Clinical trial NCT01271114: Hypertonic Saline and Terlipressin for Sepsis-associated Hypotension
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Septic Shock
Sepsis-associated Hypotension
Lead sponsor: Hospital General de Ciudad Real
Sponsor class: OTHER
Collaborators: name: University of Castilla-La Mancha
First posted: 2011-01-06
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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:

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)


Eligibility criteria: 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

Primary outcomes:
measure: MOD (Multiple Organ Dysfunction) Score
timeFrame: daily, as long as the patient stays in the ICU
Secondary outcomes:
measure: Hypertonic Saline restores IV fluid response parameters (Pulse Pressure Variation or Systolic Volume Variation) adequately
timeFrame: First 48 hours
measure: Hypertonic Saline associated with terlipressin maintains plasma sodium levels 130-155mEq/L
timeFrame: As long as Hypertonic saline plus terlipressin are in use and one week later
measure: There is an inverse relationship between plasma sodium and plasma procalcitonin levels measured by a negative Pearson coefficient
timeFrame: As long as the patient stays in the ICU
measure: Hypertonic Saline associated with terlipressin normalizes blood pressure in septic shock
timeFrame: First 48 hours
measure: Hypertonic Saline boluses increases plasma levels of vasopressin (AVP)
timeFrame: First week in ICU
measure: Hypertonic Saline use rises levels of cortisol but not of adrenocorticotropic hormone (ACTH)
timeFrame: First week in ICU
Other outcomes:
Locations:
city: Ciudad Real
country: Spain
facility: Hospital General de Ciudad Real
Study officials:
affiliation: HGCR
name: Javier Pascual Ramírez
role: PRINCIPAL_INVESTIGATOR
affiliation: HGCR
name: Luis COLLAR VIÑUELAS, MD
role: STUDY_CHAIR
References: