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

This study is currently recruiting participants.
Verified April 2013 by Hospital General de Ciudad Real
Sponsor:
Collaborator:
University of Castilla-La Mancha
Information provided by (Responsible Party):
Javier Pascual-Ramirez, Hospital General de Ciudad Real
ClinicalTrials.gov Identifier:
NCT01271114
First received: January 4, 2011
Last updated: April 22, 2013
Last verified: April 2013
History of Changes
  Purpose

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)

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Hospital General de Ciudad Real:

Primary Outcome Measures:
  • MOD (Multiple Organ Dysfunction) Score [ Time Frame: daily, as long as the patient stays in the ICU ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Hypertonic Saline restores IV fluid response parameters (Pulse Pressure Variation or Systolic Volume Variation) adequately [ Time Frame: First 48 hours ] [ Designated as safety issue: No ]
  • Hypertonic Saline associated with terlipressin maintains plasma sodium levels 130-155mEq/L [ Time Frame: As long as Hypertonic saline plus terlipressin are in use and one week later ] [ Designated as safety issue: Yes ]
  • There is an inverse relationship between plasma sodium and plasma procalcitonin levels measured by a negative Pearson coefficient [ Time Frame: As long as the patient stays in the ICU ] [ Designated as safety issue: No ]
  • Hypertonic Saline associated with terlipressin normalizes blood pressure in septic shock [ Time Frame: First 48 hours ] [ Designated as safety issue: No ]
  • Hypertonic Saline boluses increases plasma levels of vasopressin (AVP) [ Time Frame: First week in ICU ] [ Designated as safety issue: No ]
  • Hypertonic Saline use rises levels of cortisol but not of adrenocorticotropic hormone (ACTH) [ Time Frame: First week in ICU ] [ Designated as safety issue: No ]

Estimated Enrollment: 42
Study Start Date: June 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01271114

Contacts
Contact: Javier Pascual Ramírez, MD 3465451607 pascrib@hotmail.com

Locations
Spain
Hospital General de Ciudad Real Recruiting
Ciudad Real, Spain, 13005
Contact: Esperanza Segura Molina, MD     3426278000 ext 79115     eseguram@sescam.jccm.es    
Principal Investigator: Javier Pascual-Ramirez, MD            
Sub-Investigator: Luis Collar, MD            
Sub-Investigator: Alfonso Ambrós, MD            
Sub-Investigator: Francisco Araujo, Pharm D            
Sponsors and Collaborators
Hospital General de Ciudad Real
University of Castilla-La Mancha
Investigators
Principal Investigator: Javier Pascual Ramírez HGCR
Study Chair: Luis COLLAR VIÑUELAS, MD HGCR
  More Information

No publications provided

Responsible Party: Javier Pascual-Ramirez, MD, Hospital General de Ciudad Real
ClinicalTrials.gov Identifier: NCT01271114     History of Changes
Other Study ID Numbers: FISCAM AN-2010/28, 2010-024138-43
Study First Received: January 4, 2011
Last Updated: April 22, 2013
Health Authority: Spain: Spanish Agency of Medicines

Additional relevant MeSH terms:
Hypotension
Sepsis
Toxemia
Shock
Shock, Septic
Vascular Diseases
Cardiovascular Diseases
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Norepinephrine
Terlipressin
Lypressin
Sympathomimetics
 Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Antidiuretic Agents
Natriuretic Agents

ClinicalTrials.gov processed this record on May 23, 2013