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Effect of Midazolam on Inflammatory Response and Organ Function in Mechanically Ventilated Sepsis Patients With Different Immune Status

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ClinicalTrials.gov Identifier: NCT02135055
Recruitment Status : Unknown
Verified May 2014 by Xiangya Hospital of Central South University.
Recruitment status was:  Not yet recruiting
First Posted : May 9, 2014
Last Update Posted : May 9, 2014
Sponsor:
Information provided by (Responsible Party):
Xiangya Hospital of Central South University

Brief Summary:

ICU patients always experience all kinds of pain, discomfort and sleep disturbance,especially the sepsis patients. Appropriate sedation and analgesia is must,the newest sepsis guideline strongly recommend that mechanically ventilated sepsis patients need sedation therapy.

Recent studies show than immune dysfunction dose have an important effect on the occurrence and development of sepsis. When the body suffer from the pathogenic microorganism attacking and sepsis, it activate the systemic inflammatory response (SIRS) and compensatory anti-inflammatory response syndrome (CARS). When it is out of balance between SIRS and CARS, the inflammatory response, immune paralysis or immune dysfunction occurs and the mixed anti-inflammatory response syndrome (MARS) exists, and then the multiple organ dysfunction. So, immune dysfunction is thought to be the key factors on the development of the sepsis. Some studies show that the sedation drug such as midazolam, propofol, dexmedetomidine could suppress the inflammatory response effectively and then modulate the immune function.

Several recent studies show that midazolam has the immunoregulation effect and trend of suppress the inflammatory response, but the result is controversy, the possibly reason is the different immune status. Now there is the guideline about the different immune status: the normal immune function means that the value of mHLA-DR is more than 15000 monoclonal antibody; moderate-sever immune suppression means that the value of mHLA-DR is in the range of 5000 and 15000 monoclonal antibody; the immune paralysis means that the value of mHLA-DR is less than 5000 monoclonal antibody.

The purpose of the study is to explore the effect of midazolam to inflammatory response and organ function at mechanically ventilated sepsis patients who have different immune status.


Condition or disease Intervention/treatment Phase
Inflammatory Disorder of Immune System Sepsis Other: blood sample collection Drug: Midazolam Drug: Morphine Procedure: Sedation interruption Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effect of Midazolam on Inflammatory Response and Organ Function in Mechanically Ventilated Sepsis Patients With Different Immune Status.
Study Start Date : May 2014
Estimated Primary Completion Date : March 2015
Estimated Study Completion Date : March 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sepsis

Arm Intervention/treatment
Experimental: Normal immune function
The value of monocyte human leukocyte antigen-DR (mHLA-DR) is equal to or more than 15000 monoclonal antibody.
Other: blood sample collection
Patients were included 1 hrs later(before the study drug is administrated), 3 d and 7 d after sedation with midazolam, blood sample is collected. Flow cytometry is performed to test the mHLA-DR and according the value of mHLA-DR, assign the participant to the 4 groups as described in the arm.

Drug: Midazolam
The loading dose of midazolam is 0.03-0.3 mg/kg, intravenous injected slowly for 10 minutes, then 0.04-0.2 mg/kg/h for maintenance of sedation.
Other Name: Liyuexi

Drug: Morphine
Morphine is the only analgesic drug that permitted to use. 2 mg morphine is given a bolus when the participant feel pain. If the pain is not alleviated, 0.4-1 mg/h morphine is maintained.

Procedure: Sedation interruption
Sedation interruption is performed at 8 am every morning.

Experimental: Moderate immunosuppression
The value of mHLA-DR is equal to or more than 10000 and less than 15000 monoclonal antibody.
Other: blood sample collection
Patients were included 1 hrs later(before the study drug is administrated), 3 d and 7 d after sedation with midazolam, blood sample is collected. Flow cytometry is performed to test the mHLA-DR and according the value of mHLA-DR, assign the participant to the 4 groups as described in the arm.

Drug: Midazolam
The loading dose of midazolam is 0.03-0.3 mg/kg, intravenous injected slowly for 10 minutes, then 0.04-0.2 mg/kg/h for maintenance of sedation.
Other Name: Liyuexi

Drug: Morphine
Morphine is the only analgesic drug that permitted to use. 2 mg morphine is given a bolus when the participant feel pain. If the pain is not alleviated, 0.4-1 mg/h morphine is maintained.

Procedure: Sedation interruption
Sedation interruption is performed at 8 am every morning.

Experimental: Sever immunosuppression
The value of mHLA-DR is equal to or more than 5000 and less than 10000 monoclonal antibody.
Other: blood sample collection
Patients were included 1 hrs later(before the study drug is administrated), 3 d and 7 d after sedation with midazolam, blood sample is collected. Flow cytometry is performed to test the mHLA-DR and according the value of mHLA-DR, assign the participant to the 4 groups as described in the arm.

Drug: Midazolam
The loading dose of midazolam is 0.03-0.3 mg/kg, intravenous injected slowly for 10 minutes, then 0.04-0.2 mg/kg/h for maintenance of sedation.
Other Name: Liyuexi

Drug: Morphine
Morphine is the only analgesic drug that permitted to use. 2 mg morphine is given a bolus when the participant feel pain. If the pain is not alleviated, 0.4-1 mg/h morphine is maintained.

Procedure: Sedation interruption
Sedation interruption is performed at 8 am every morning.

Experimental: Immune paralysis
The value of mHLA-DR is less than 5000 monoclonal antibody.
Other: blood sample collection
Patients were included 1 hrs later(before the study drug is administrated), 3 d and 7 d after sedation with midazolam, blood sample is collected. Flow cytometry is performed to test the mHLA-DR and according the value of mHLA-DR, assign the participant to the 4 groups as described in the arm.

Drug: Midazolam
The loading dose of midazolam is 0.03-0.3 mg/kg, intravenous injected slowly for 10 minutes, then 0.04-0.2 mg/kg/h for maintenance of sedation.
Other Name: Liyuexi

Drug: Morphine
Morphine is the only analgesic drug that permitted to use. 2 mg morphine is given a bolus when the participant feel pain. If the pain is not alleviated, 0.4-1 mg/h morphine is maintained.

Procedure: Sedation interruption
Sedation interruption is performed at 8 am every morning.




Primary Outcome Measures :
  1. T cell subset T Helper 1 [ Time Frame: Change from baseline of T Helper 1 at 3 and 7 days. ]

    T Helper 1(TH1) are tested before sedation, 3 d and 7 d after sedation with midazolam.

    The test method is Flow cytometry.


  2. T cell subset T Helper 2 [ Time Frame: Change from baseline of T Helper 2 at 3 and 7 days. ]

    T Helper 2(TH2) are tested before sedation, 3 d and 7 d after sedation with midazolam.

    The test method is Flow cytometry.


  3. T cell subset Regulatory T Cell [ Time Frame: Change from baseline of Regulatory T Cell at 3 and 7 days. ]

    Regulatory T Cell are tested before sedation, 3 d and 7 d after sedation with midazolam.

    The test method is Flow cytometry.


  4. Interleukin-6 [ Time Frame: Change from baseline of Interleukin-6 at 3 and 7 days. ]

    Levels of interleukin-6(IL-6) are tested before sedation, 3 d and 7 d after sedation with midazolam.

    The test method is Enzyme Linked Immunosorbent Assay(ELISA).


  5. Interleukin-10 [ Time Frame: Change from baseline of Interleukin-10 at 3 and 7 days. ]

    Levels of interleukin-10(IL-10) are tested before sedation, 3 d and 7 d after sedation with midazolam.

    The test method is Enzyme Linked Immunosorbent Assay(ELISA).


  6. Tumo necrosis factor-α(TNF-α) [ Time Frame: Change from baseline of TNF-α at 3 and 7 days. ]

    Levels of Tumo necrosis factor-α(TNF-α) are tested before sedation, 3 d and 7 d after sedation with midazolam.

    The test method is Enzyme Linked Immunosorbent Assay(ELISA).



Secondary Outcome Measures :
  1. duration of mechanical ventilation [ Time Frame: from the begining of ventilation to weaning, up to 7 days. ]
  2. Number of Participants with Serious and Non-Serious Adverse Events [ Time Frame: up to 7 days ]
  3. Mortality [ Time Frame: up to 28 days ]
    Participants' mortality of 28 and 90 days is recorded, including state of survival, the date and the reason of death.

  4. Length of ICU stay [ Time Frame: from ICU admmittion to discharge from ICU,up to 28 days. ]
  5. Index of renal function [ Time Frame: baseline,the 3rd and 7th day after sedation ]
    level of Blood Urea Nitrogen(BUN) and Creatinine(Cr).

  6. Index of myocardial enzyme [ Time Frame: baseline,the 3rd and 7th day after sedation ]
    level of Brain Natriuretic Peptide(BNP).

  7. Index of hepatic function [ Time Frame: baseline,the 3rd and 7th day after sedation ]
    level of glutamic-pyruvic transaminase(ALT),glutamic oxalacetic transaminase(AST),Total Bilirubin(Tbil).

  8. Index of endocrine function [ Time Frame: baseline,the 3rd and 7th day after sedation ]
    level of cortisol and blood glucose.

  9. C-reaction protein [ Time Frame: baseline,the 3rd and 7th day after sedation ]

    C-reaction protein(CRP)is tested before sedation, 3 d and 7 d after sedation with midazolam.

    The test method is Enzyme Linked Immunosorbent Assay(ELISA).



Other Outcome Measures:
  1. mHLA-DR [ Time Frame: baseline,the 3rd and 7th day after sedation ]

    Levels of mHLA-DR are tested before sedation, 3 d and 7 d after sedation with midazolam.

    The test method is Flow cytometry.




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Mechanically ventilated ICU patients, sedation is needed.
  2. Sepsis patients.
  3. Age 18-80 yrs
  4. Anticipated sedation duration is more than 3 days.
  5. Agreed to participate the study and assigned the informed consent. -

Exclusion Criteria:

  1. Allergic to the Benzodiazepine.
  2. Hepatic dysfunction(Child-Pugh is C level).
  3. Participated other study.
  4. Bad prognosis and possibly become the major reason of patients death, such as sever craniocerebral injury,cardiopulmonary resuscitation,advanced malignant tumor,etc.
  5. History of immune system disease, immune treatment (including hormone ) or treatment that could affect immune function (including continuous renal replacement therapy,CRRT).
  6. Alcoholic and drug abuse.
  7. Tendency for major mental disease or treatment of anti psychotics.
  8. Pregnant,lactation woman.
  9. Unwilling to assign the informed consent or bad compliance. -

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02135055


Sponsors and Collaborators
Xiangya Hospital of Central South University
Investigators
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Principal Investigator: Yuhang Ai, Doctor. Xiangya Hospital of Central South University

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Responsible Party: Xiangya Hospital of Central South University
ClinicalTrials.gov Identifier: NCT02135055    
Other Study ID Numbers: 2014021801
First Posted: May 9, 2014    Key Record Dates
Last Update Posted: May 9, 2014
Last Verified: May 2014
Keywords provided by Xiangya Hospital of Central South University:
organ function
sedation
Additional relevant MeSH terms:
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Sepsis
Toxemia
Immune System Diseases
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Midazolam
Morphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adjuvants, Anesthesia
Hypnotics and Sedatives
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action