The Effect of Dexmedetomidine on Microcirculation in Severe Sepsis

NCT02109965 | Terminated Phase 4 DMC

• 1 other identifier: 201311031MINB
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Despite early goal-directed maintenance of normal macrocirculation, the reduction of 60-day mortality of patients with severe sepsis and septic shock remained unsatisfied (56.9% to 44.3%). One of the major causes of high mortality is microcirculatory dysfunction. Delayed diagnosis and treatment of microcirculatory dysfunction may cause tissue hypoperfusion and resulted in multiple organ dysfunction and death. Dexmedetomidine is a highly selective α2-adrenoreceptor agonist which exhibits sedative and analgesic effects. Recent studies suggest that dexmedetomidine also has anti-coagulation and anti-inflammatory effects, and it can reduce the mortality of endotoxemic rats and patients with severe sepsis. The investigators will conduct two animal studies and one clinical trial to investigate the effect of dexmedetomidine on microcirculatory dysfunction and organ injury in rat with endotoxemia and patients with severe sepsis and septic shock. Sixty patients with severe sepsis and septic shock will be enrolled and randomized to control group or dexmedetomidine group. In the control group, the patients will be treated according to the clinical practice guideline. If sedation is required, non-dexmedetomidine sedative agents will be used. In the dexmedetomidine group, the patients will be treated according to the clinical practice guideline, and they will also receive continuous infusion of dexmedetomidine (infusion rate ranged from 0.1 to 0.7 mcg/kg/h) for 24 hours as needed. The sublingual microcirculation, serum level of Endocan, NGAL(Neutrophil Gelatinase-Associated Lipocalin), and BNP(B-type natriuretic peptide) will be examined at preset time points up to 24 hours. The vital signs, hemodynamic parameters, and survival of 28-day and 90-day will be recorded and analyzed.

Conditions

Severe Sepsis

Outcome Measures

Primary Outcomes (1)

• Changes of total small vessel density and perfused small vessel density

  6h

Secondary Outcomes (2)

• Changes of total small vessel density and perfused small vessel density

  24h

• Change of microvascular flow index

  6h and 24h

Other Outcomes (4)

• Endocan level

  24h

• Hemodynamic variables

  6h and 24h

• NGAL level

  6h and 24h

Study Arms (2)

Control

ACTIVE COMPARATOR

Use midazolam or propofol for sedation

Drug: Midazolam; Drug: Propofol

Dexmedetomidine

EXPERIMENTAL

Use dexmedetomidine for sedation

Drug: Dexmedetomidine

Interventions

Dexmedetomidine DRUG

Continue infusion (CIF) 0.1 - 0.7 mcg/kg/h Goal of sedation: Richmonad agitation-sedation scale 0 to -2

Also known as: Precedex

Dexmedetomidine

Midazolam DRUG

CIF Goal of sedation: Richmonad agitation-sedation scale 0 to -2

Also known as: Dormicium

Control

Propofol DRUG

CIF Goal of sedation: Richmonad agitation-sedation scale 0 to -2

Also known as: Propofol-Lipuro

Control

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ICU patients who require sedation
• Patients who have diagnosis of severe sepsis / septic shock
• meet 2 or more of the 4 SIRS criteria
• with one organ dysfunction according the definition of Surviving Sepsis Campaign

You may not qualify if:

• less than 20 y/o
• refractory bradycardia (heart rate slower than 60 bpm despite of adequate treatment)
• nd and 3rd degree of AV-block
• the onset of severe sepsis/septic shock is more than 24h before enrollment
• APACHE II \> 30 at enrollment
• Severe liver cirrhosis (Child B or C)
• New onset of myocardial infarction within 30 days or heart failure (NYHA 4)
• attend other trial in ICU within one month
• patient who is pregnant
• receive organ transplantation within one year
• expected survival is less than 30 days by attending physician
• receive cardiopulmonary resuscitation within 4 weeks
• patients who have signed consent of refusal of cardiopulmonary resuscitation and invasive therapy
• have allergic history to dexmedetomidine
• receive renal replacement therapy within 24 hours before enrollment

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

MeSH Terms

Conditions

Sepsis

Interventions

Dexmedetomidine; Midazolam; Propofol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Yu-Chang Yeh, MD, PhD

  National Taiwan University Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2014
• First Posted: April 10, 2014
• Study Start: July 1, 2014
• Primary Completion: February 24, 2016
• Study Completion: February 24, 2018
• Last Updated: March 4, 2019

Record last verified: 2019-02

Locations

TW (1)