Hypertonic Saline and Terlipressin for Sepsis-associated Hypotension

NCT ID: NCT01271114

Last Updated: 2014-03-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2013-12-31

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)

Conditions

Septic Shock; Sepsis-associated Hypotension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Hypertonic Saline and Terlipressin

Group Type: EXPERIMENTAL

Hypertonic Saline and Terlipressin

Intervention Type: 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

Normal Saline and norepinephrine

Group Type: ACTIVE_COMPARATOR

Normal saline and norepinephrine

Intervention Type: 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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Castilla-La Mancha

OTHER

Sponsor Role: collaborator

Hospital General de Ciudad Real

OTHER

Sponsor Role: lead

Responsible Party

Javier Pascual-Ramirez

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Javier Pascual Ramírez

Role: PRINCIPAL_INVESTIGATOR

HGCR

Luis COLLAR VIÑUELAS, MD

Role: STUDY_CHAIR

HGCR

Locations

Hospital General de Ciudad Real

Ciudad Real, Ciudad Real, Spain

Countries

Spain

Other Identifiers

2010-024138-43

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

FISCAM AN-2010/28

Identifier Type: -

Identifier Source: org_study_id