Inflammatory Disorder of Immune SystemPhase 4NCT02135055
Effect of Midazolam on Inflammatory Response and Organ Function in Mechanically Ventilated Sepsis Patients With Different Immune Status
A Phase 4 study testing blood sample collection, Midazolam and Morphine in people with Inflammatory Disorder of Immune System and Sepsis, run by Xiangya Hospital of Central South University.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Inflammatory Disorder of Immune System, Sepsis
- What is being tested?
- blood sample collection, Midazolam and Morphine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- No sites listed yet
- Study dates
- May 2014to Mar 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Mechanically ventilated ICU patients, sedation is needed.
- Sepsis patients.
- Age 18-80 yrs
- Anticipated sedation duration is more than 3 days.
- Agreed to participate the study and assigned the informed consent. -
Who cannot join
- Allergic to the Benzodiazepine.
- Hepatic dysfunction(Child-Pugh is C level).
- Participated other study.
- Bad prognosis and possibly become the major reason of patients death, such as sever craniocerebral injury,cardiopulmonary resuscitation,advanced malignant tumor,etc.
- History of immune system disease, immune treatment (including hormone ) or treatment that could affect immune function (including continuous renal replacement therapy,CRRT).
- Alcoholic and drug abuse.
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- Tendency for major mental disease or treatment of anti psychotics.
- Pregnant,lactation woman.
- Unwilling to assign the informed consent or bad compliance. -
About this study
Official title: Effect of Midazolam on Inflammatory Response and Organ Function in Mechanically Ventilated Sepsis Patients With Different Immune Status.
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.
Read more
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.
- Conditions
- Inflammatory Disorder of Immune System, Sepsis
- Keywords
- organ function, sedation
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood sample collectionOther
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.
MidazolamDrug
Also called Liyuexi
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.
MorphineDrug
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.
Sedation interruptionProcedure or surgery
Sedation interruption is performed at 8 am every morning.
| Study group | Role | What they receive |
|---|---|---|
| Normal immune function | Experimental | The value of monocyte human leukocyte antigen-DR (mHLA-DR) is equal to or more than 15000 monoclonal antibody. Receives: Other: blood sample collection; Drug: Midazolam; Drug: Morphine; Procedure: Sedation interruption |
| Moderate immunosuppression | Experimental | The value of mHLA-DR is equal to or more than 10000 and less than 15000 monoclonal antibody. Receives: Other: blood sample collection; Drug: Midazolam; Drug: Morphine; Procedure: Sedation interruption |
| Sever immunosuppression | Experimental | The value of mHLA-DR is equal to or more than 5000 and less than 10000 monoclonal antibody. Receives: Other: blood sample collection; Drug: Midazolam; Drug: Morphine; Procedure: Sedation interruption |
| Immune paralysis | Experimental | The value of mHLA-DR is less than 5000 monoclonal antibody. Receives: Other: blood sample collection; Drug: Midazolam; Drug: Morphine; Procedure: Sedation interruption |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Change from baseline of T Helper 1 at 3 and 7 days.
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.
Measured: Change from baseline of T Helper 2 at 3 and 7 days.
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.
Measured: Change from baseline of Regulatory T Cell at 3 and 7 days.
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）.
Measured: Change from baseline of Interleukin-6 at 3 and 7 days.
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）.
Measured: Change from baseline of Interleukin-10 at 3 and 7 days.
Tumo necrosis factor-α(TNF-α)
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）.
Measured: Change from baseline of TNF-α at 3 and 7 days.
Secondary outcomes (9)
duration of mechanical ventilation
Measured: from the begining of ventilation to weaning, up to 7 days.
Number of Participants with Serious and Non-Serious Adverse Events
Measured: up to 7 days
Mortality
Participants' mortality of 28 and 90 days is recorded, including state of survival, the date and the reason of death.
Measured: up to 28 days
Length of ICU stay
Measured: from ICU admmittion to discharge from ICU,up to 28 days.
Index of renal function
level of Blood Urea Nitrogen(BUN) and Creatinine(Cr).
Measured: baseline,the 3rd and 7th day after sedation
Index of myocardial enzyme
level of Brain Natriuretic Peptide(BNP).
Measured: baseline,the 3rd and 7th day after sedation
Index of hepatic function
level of glutamic-pyruvic transaminase(ALT),glutamic oxalacetic transaminase(AST),Total Bilirubin(Tbil).
Measured: baseline,the 3rd and 7th day after sedation
Index of endocrine function
level of cortisol and blood glucose.
Measured: baseline,the 3rd and 7th day after sedation
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）.
Measured: baseline,the 3rd and 7th day after sedation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2014 (estimated)
- Study startMay 2014
- Primary completionMar 2015 (estimated)
- Study completionMar 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Inflammatory Disorder of Immune SystemStudies of the same condition, open and under way.
- More trials run by Xiangya Hospital of Central South UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xiangya Hospital of Central South University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yuhang Ai, Doctor., Principal investigator, Xiangya Hospital of Central South University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02135055
- Sponsor's protocol ID
- 2014021801
- Status last verified
- May 2014
- First submitted
- 29 Apr 2014
- Last updated
- 9 May 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Midazolam on Inflammatory Response and Organ Function in Mechanically Ventilated Sepsis Patients With Different Immune Status.
- ClinicalTrials.gov ID
- NCT02135055
- Acronym / sponsor ID
- 2014021801
- Conditions
- Inflammatory Disorder of Immune System, Sepsis
- Keywords
- organ function, sedation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Xiangya Hospital of Central South UniversityUniversity, hospital or other
- Study start
- May 2014
- Primary completion
- Mar 2015 (estimated)
- Study completion
- Mar 2015 (estimated)
- First posted
- 9 May 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Normal immune function | Experimental | Other: blood sample collection, Drug: Midazolam, Drug: Morphine, Procedure: Sedation interruptionThe value of monocyte human leukocyte antigen-DR (mHLA-DR) is equal to or more than 15000 monoclonal antibody. |
| Moderate immunosuppression | Experimental | Other: blood sample collection, Drug: Midazolam, Drug: Morphine, Procedure: Sedation interruptionThe value of mHLA-DR is equal to or more than 10000 and less than 15000 monoclonal antibody. |
| Sever immunosuppression | Experimental | Other: blood sample collection, Drug: Midazolam, Drug: Morphine, Procedure: Sedation interruptionThe value of mHLA-DR is equal to or more than 5000 and less than 10000 monoclonal antibody. |
| Immune paralysis | Experimental | Other: blood sample collection, Drug: Midazolam, Drug: Morphine, Procedure: Sedation interruptionThe value of mHLA-DR is less than 5000 monoclonal antibody. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Mechanically ventilated ICU patients, sedation is needed.
- Sepsis patients.
- Age 18-80 yrs
- Anticipated sedation duration is more than 3 days.
- Agreed to participate the study and assigned the informed consent. -
Key exclusion criteria (9 listed)
- Allergic to the Benzodiazepine.
- Hepatic dysfunction(Child-Pugh is C level).
- Participated other study.
- Bad prognosis and possibly become the major reason of patients death, such as sever craniocerebral injury,cardiopulmonary resuscitation,advanced malignant tumor,etc.
- History of immune system disease, immune treatment (including hormone ) or treatment that could affect immune function (including continuous renal replacement therapy,CRRT).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood sample collectionPatients 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. | Other | Immune paralysis, Moderate immunosuppression, Normal immune function, Sever immunosuppression |
| MidazolamAlso: LiyuexiThe 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. | Drug | Immune paralysis, Moderate immunosuppression, Normal immune function, Sever immunosuppression |
| MorphineMorphine 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. | Drug | Immune paralysis, Moderate immunosuppression, Normal immune function, Sever immunosuppression |
| Sedation interruptionSedation interruption is performed at 8 am every morning. | Procedure or surgery | Immune paralysis, Moderate immunosuppression, Normal immune function, Sever immunosuppression |
Primary outcome
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.
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.
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.
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）.
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）.
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）.
9 secondary outcomes
duration of mechanical ventilation
Time frame: from the begining of ventilation to weaning, up to 7 days.
Number of Participants with Serious and Non-Serious Adverse Events
Time frame: up to 7 days
Mortality
Time frame: up to 28 days
Length of ICU stay
Time frame: from ICU admmittion to discharge from ICU,up to 28 days.
Index of renal function
Time frame: baseline,the 3rd and 7th day after sedation
Index of myocardial enzyme
Time frame: baseline,the 3rd and 7th day after sedation
Index of hepatic function
Time frame: baseline,the 3rd and 7th day after sedation
Index of endocrine function
Time frame: baseline,the 3rd and 7th day after sedation
C-reaction protein
Time frame: baseline,the 3rd and 7th day after sedation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yuhang Ai, Doctor. principal investigator
Xiangya Hospital of Central South University
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing blood sample collection, Midazolam and Morphine in people with Inflammatory Disorder of Immune System and Sepsis, run by Xiangya Hospital of Central South University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 May 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
T cell subset T Helper 1 (time frame: Change from baseline of T Helper 1 at 3 and 7 days.). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2014.