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

Sepsis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02135055
• Other study ID #: 2014021801
• Status: Not yet recruiting
• Phase: Phase 4
• First received: April 29, 2014
• Last updated: May 7, 2014
• Start date: May 2014
• Est. completion date: March 2015

Study information

• Verified date: May 2014
• Source: Xiangya Hospital of Central South University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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. -

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Immune System Diseases
• Inflammatory Disorder of Immune System
• Sepsis

Intervention

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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Xiangya Hospital of Central South University

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	mHLA-DR	Levels of mHLA-DR are tested before sedation, 3 d and 7 d after sedation with midazolam.; The test method is Flow cytometry.	baseline,the 3rd and 7th day after sedation	No
Primary	T cell subset T Helper 1	T Helper 1(TH1) are tested before sedation, 3 d and 7 d after sedation with midazolam.; The test method is Flow cytometry.	Change from baseline of T Helper 1 at 3 and 7 days.	No
Primary	T cell subset T Helper 2	T Helper 2(TH2) are tested before sedation, 3 d and 7 d after sedation with midazolam.; The test method is Flow cytometry.	Change from baseline of T Helper 2 at 3 and 7 days.	No
Primary	T cell subset Regulatory T Cell	Regulatory T Cell are tested before sedation, 3 d and 7 d after sedation with midazolam.; The test method is Flow cytometry.	Change from baseline of Regulatory T Cell at 3 and 7 days.	No
Primary	Interleukin-6	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).	Change from baseline of Interleukin-6 at 3 and 7 days.	No
Primary	Interleukin-10	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).	Change from baseline of Interleukin-10 at 3 and 7 days.	No
Primary	Tumo necrosis factor-a(TNF-a)	Levels of Tumo necrosis factor-a(TNF-a) are tested before sedation, 3 d and 7 d after sedation with midazolam.; The test method is Enzyme Linked Immunosorbent Assay(ELISA).	Change from baseline of TNF-a at 3 and 7 days.	No
Secondary	duration of mechanical ventilation		from the begining of ventilation to weaning, up to 7 days.	No
Secondary	Number of Participants with Serious and Non-Serious Adverse Events		up to 7 days	Yes
Secondary	Mortality	Participants' mortality of 28 and 90 days is recorded, including state of survival, the date and the reason of death.	up to 28 days	Yes
Secondary	Length of ICU stay		from ICU admmittion to discharge from ICU,up to 28 days.	No
Secondary	Index of renal function	level of Blood Urea Nitrogen(BUN) and Creatinine(Cr).	baseline,the 3rd and 7th day after sedation	No
Secondary	Index of myocardial enzyme	level of Brain Natriuretic Peptide(BNP).	baseline,the 3rd and 7th day after sedation	No
Secondary	Index of hepatic function	level of glutamic-pyruvic transaminase(ALT),glutamic oxalacetic transaminase(AST),Total Bilirubin(Tbil).	baseline,the 3rd and 7th day after sedation	No
Secondary	Index of endocrine function	level of cortisol and blood glucose.	baseline,the 3rd and 7th day after sedation	No
Secondary	C-reaction protein	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).	baseline,the 3rd and 7th day after sedation	No