Hypertonic Saline and Terlipressin for Sepsis-associated Hypotension

NCT01271114 | Terminated Phase 3 DMC

• 2 other identifiers: FISCAM AN-2010/282010-024138-43
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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

Conditions

Septic Shock; Sepsis-associated Hypotension

Outcome Measures

Primary Outcomes (1)

• MOD (Multiple Organ Dysfunction) Score

  daily, as long as the patient stays in the ICU

Secondary Outcomes (6)

• 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

Study Arms (2)

Hypertonic Saline and Terlipressin

EXPERIMENTAL

Drug: Hypertonic Saline and Terlipressin

Normal Saline and norepinephrine

ACTIVE COMPARATOR

Drug: Normal saline and norepinephrine

Interventions

Hypertonic Saline and Terlipressin DRUG

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

Hypertonic Saline and Terlipressin

Normal saline and norepinephrine DRUG

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

Normal Saline and norepinephrine

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospital General de Ciudad Real: lead
• University of Castilla-La Mancha: collaborator

Study Sites (1)

Hospital General de Ciudad Real

Ciudad Real, Ciudad Real, 13005, Spain

Location

MeSH Terms

Conditions

Shock, Septic

Interventions

Saline Solution, Hypertonic; Terlipressin; Saline Solution; Norepinephrine

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Hypertonic Solutions; Solutions; Pharmaceutical Preparations; Lypressin; Vasopressins; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Crystalloid Solutions; Isotonic Solutions; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Javier Pascual Ramírez

  HGCR

  PRINCIPAL INVESTIGATOR

• Luis COLLAR VIÑUELAS, MD

  HGCR

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 4, 2011
• First Posted: January 6, 2011
• Study Start: June 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: March 10, 2014

Record last verified: 2014-03

Locations

ES (1)