Upregulation of Alpha-1 Receptors Upon Septic Shock?

Phase 2

Terminated

• Conditions: Septic Shock
• Interventions: Drug: Placebo; Drug: Clonidine

• Registration Number: NCT01856517
• Lead Sponsor: Direction Centrale du Service de Santé des Armées

Brief Summary

The hallmarks of septic shock are hypovolemia and reduced pressor response to endogenous noradrenaline. The working hypothesis is that the higher the plasma concentration of endogenous noradrenaline will be, the lower the pressor response to exogenous noradrenaline will be. This will be tested in patients presenting with septic shock, following state of the art management (including repeated assessment of vena cava diameter and compliance, and response to dynamic indices of loading) following placebo vs clonidine administration (1 mcg.kg-1.h-1 over 24 h without bolus) and administration of increasing doses of noradrenaline (1 mcg, 2 mcg, etc. up to a delta systolic blood pressure circa 25-30 mm Hg).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-04-19
• Study First Submitted QC: 2013-05-16
• Study First Posted: 2013-05-17
• Study Start: 2013-08
• Primary Completion: 2013-08
• Study Completion: 2014-09
• Status Verified: 2017-07
• Last Update Submitted: 2017-07-26
• Last Update Posted: 2017-07-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• patients presenting to the CCU with septic shock : SBP<90 mm Hg refractory to volume load (>30 ml.kg-1 within 6 h before inclusion) thus in need administration of noradrenaline for >1 h (0.1 mcg.kg-1.h-1 i.e. >0.5 mg.h-1/70 kg) to maintain mean BP>65 mm Hg.
• criteria for sepsis :temperature>38.5 or <36°C ; WBC>12 000 or <4000/ml ; tachypnea (>20 cycles par min) or mechanical ventilation ; tachycardia : >90 bpmin
• written informed consent by the patient or next of kin or signature by the investigators of the form "emergency inclusion"

Exclusion Criteria

• age<18 ans
• pregnancy
• mental illness making informed consent impossible
• Absence of consent as signed by the patient or next of kin or signature of "emergency inclusion form"
• individual without social security coverage or participating in another biomedical research
• Contre-indications to clonidine (uncorrected hypovolemia, sick sinus syndrom, III grade AV block)
• HR<70 bp/min
• pre-exitus

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	Placebo	saline administration over 24 h following full optimization of patient according to current guidelines
clonidine	Clonidine	clonidine 1 mcg.kg-1.h-1 over 24 h following full optimization of the patient according to current guidelines

Primary Outcome Measures

Name	Time	Method
change in pressor response to exogenous noradrenaline	0 and 24 h	bolus of exogenous noradrenaline (1 mcg and up) are administered to the patient to evoke an increase in delta systolic blood pressure by 25-30 mm Hg. Administration of increasing dose of noradrenaline is stopped as soon as delta systolic blood pressure has reached 25-30 mm Hg.

Secondary Outcome Measures

Name	Time	Method
change in heart rate response to increasing doses of dobutamine (100 mcg and up) to evoke an increase in heart rate up to 20 beats per min.	0 and 24 h

Trial Locations

Locations (1)

Critical Care Unit, Hopital Desgenettes; 🇫🇷 Lyon, France