Brief Summary
This study evaluates whether giving a neuromuscular blocker (skeletal muscle relaxant) to a patient with acute respiratory distress syndrome will improve survival. Half of the patients will receive a neuromuscular blocker for two days and in the other half the use of neuromuscular blockers will be discouraged.
Brief Title
Reevaluation Of Systemic Early Neuromuscular Blockade
Detailed Description
PRIMARY OBJECTIVE:
To assess the efficacy and safety of early neuromuscular blockade in reducing mortality and morbidity in patients with moderate-severe ARDS, in comparison to a control group with no routine early neuromuscular blockade (NMB).
PRIMARY HYPOTHESIS:
Early neuromuscular blockade will improve mortality prior to discharge home before day 90, in patients with moderate-severe ARDS.
The trial will accrue a maximum of 1408 patients. Patients will be recruited from the emergency departments, intensive care units and other acute care areas of the PETAL Network Clinical Centers and randomized to the active (NMB) or control. The overall strategy is to screen, consent, and enroll early, every newly intubated, acutely ill or post-operative, eligible patient at each site, using clinically obtained pulse oximetry and blood gases.
By preventing active expiration, and/or patient ventilator dyssynchrony, neuromuscular blockade may create a more homogenous distribution of airway pressures and tidal volumes, preventing barotrauma/volutrauma and "atelectrauma" resulting in less ventilator-induced lung injury.
To assess the efficacy and safety of early neuromuscular blockade in reducing mortality and morbidity in patients with moderate-severe ARDS, in comparison to a control group with no routine early neuromuscular blockade (NMB).
PRIMARY HYPOTHESIS:
Early neuromuscular blockade will improve mortality prior to discharge home before day 90, in patients with moderate-severe ARDS.
The trial will accrue a maximum of 1408 patients. Patients will be recruited from the emergency departments, intensive care units and other acute care areas of the PETAL Network Clinical Centers and randomized to the active (NMB) or control. The overall strategy is to screen, consent, and enroll early, every newly intubated, acutely ill or post-operative, eligible patient at each site, using clinically obtained pulse oximetry and blood gases.
By preventing active expiration, and/or patient ventilator dyssynchrony, neuromuscular blockade may create a more homogenous distribution of airway pressures and tidal volumes, preventing barotrauma/volutrauma and "atelectrauma" resulting in less ventilator-induced lung injury.
Completion Date
Completion Date Type
Actual
Conditions
Acute Respiratory Distress Syndrome
Eligibility Criteria
Inclusion Criteria
1. Age \> 18 years
2. Presence of all of the following conditions for \< 48 hours:
i. PaO2/FiO2 \< 150 with PEEP \>/= 8 cm H2O OR, if ABG not available, SaO2/FiO2 ratio that is equivalent to a PaO2/FiO2 \< 150 with PEEP \>/= 8 cm H2O , and a confirmatory SaO2/FiO2 ratio that is again equivalent 1-6 hours later
ii. Bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules.
iii. Respiratory failure not fully explained by cardiac failure or fluid overload; need objective assessment (e.g., echocardiography) to exclude hydrostatic edema if no risk factor present.
Patients must be enrolled within 48 hours of meeting inclusion criteria.
Exclusion Criteria:
1. Lack of informed consent
2. Continuous neuromuscular blockade at enrollment
3. Known pregnancy
4. Currently receiving ECMO therapy
5. Chronic respiratory failure defined as PaCO2 \> 60 mm Hg in the outpatient setting
6. Home mechanical ventilation (non-invasive ventilation or via tracheotomy) except for CPAP/BIPAP used solely for sleep-disordered breathing
7. Actual body weight exceeding 1 kg per centimeter of height
8. Severe chronic liver disease defined as a Child-Pugh score of 12-15 (Appendix A2)
9. Bone marrow transplantation within the last 1 year
10. Expected duration of mechanical ventilation of \< 48 hours
11. Decision to withhold life-sustaining treatment; except in those patients committed to full support except cardiopulmonary resuscitation if an actual cardiac arrest occurs
12. Moribund patient not expected to survive 24 hours; if CPR provided, assess for moribund status greater than 6 from CPR conclusion
13. Diffuse alveolar hemorrhage from vasculitis
14. Burns \> 70% total body surface
15. Unwillingness to utilize the ARDS Network 6 ml/kg IBW ventilation protocol
16. Previous hypersensitivity or anaphylactic reaction to cisatracurium
17. Neuromuscular conditions that may potentiate neuromuscular blockade and/or impair spontaneous ventilation (Appendix A2)
18. Neurologic conditions undergoing treatment for intracranial hypertension
19. Enrollment in an interventional ARDS trial with direct impact on neuromuscular blockade and PEEP
20. \>120 hours of mechanical ventilation
21. P/F \< 200 mmHg at the time of randomization (if available)
1. Age \> 18 years
2. Presence of all of the following conditions for \< 48 hours:
i. PaO2/FiO2 \< 150 with PEEP \>/= 8 cm H2O OR, if ABG not available, SaO2/FiO2 ratio that is equivalent to a PaO2/FiO2 \< 150 with PEEP \>/= 8 cm H2O , and a confirmatory SaO2/FiO2 ratio that is again equivalent 1-6 hours later
ii. Bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules.
iii. Respiratory failure not fully explained by cardiac failure or fluid overload; need objective assessment (e.g., echocardiography) to exclude hydrostatic edema if no risk factor present.
Patients must be enrolled within 48 hours of meeting inclusion criteria.
Exclusion Criteria:
1. Lack of informed consent
2. Continuous neuromuscular blockade at enrollment
3. Known pregnancy
4. Currently receiving ECMO therapy
5. Chronic respiratory failure defined as PaCO2 \> 60 mm Hg in the outpatient setting
6. Home mechanical ventilation (non-invasive ventilation or via tracheotomy) except for CPAP/BIPAP used solely for sleep-disordered breathing
7. Actual body weight exceeding 1 kg per centimeter of height
8. Severe chronic liver disease defined as a Child-Pugh score of 12-15 (Appendix A2)
9. Bone marrow transplantation within the last 1 year
10. Expected duration of mechanical ventilation of \< 48 hours
11. Decision to withhold life-sustaining treatment; except in those patients committed to full support except cardiopulmonary resuscitation if an actual cardiac arrest occurs
12. Moribund patient not expected to survive 24 hours; if CPR provided, assess for moribund status greater than 6 from CPR conclusion
13. Diffuse alveolar hemorrhage from vasculitis
14. Burns \> 70% total body surface
15. Unwillingness to utilize the ARDS Network 6 ml/kg IBW ventilation protocol
16. Previous hypersensitivity or anaphylactic reaction to cisatracurium
17. Neuromuscular conditions that may potentiate neuromuscular blockade and/or impair spontaneous ventilation (Appendix A2)
18. Neurologic conditions undergoing treatment for intracranial hypertension
19. Enrollment in an interventional ARDS trial with direct impact on neuromuscular blockade and PEEP
20. \>120 hours of mechanical ventilation
21. P/F \< 200 mmHg at the time of randomization (if available)
Inclusion Criteria
Inclusion Criteria
1. Age \> 18 years
2. Presence of all of the following conditions for \< 48 hours:
i. PaO2/FiO2 \< 150 with PEEP \>/= 8 cm H2O OR, if ABG not available, SaO2/FiO2 ratio that is equivalent to a PaO2/FiO2 \< 150 with PEEP \>/= 8 cm H2O , and a confirmatory SaO2/FiO2 ratio that is again equivalent 1-6 hours later
ii. Bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules.
iii. Respiratory failure not fully explained by cardiac failure or fluid overload; need objective assessment (e.g., echocardiography) to exclude hydrostatic edema if no risk factor present.
Patients must be enrolled within 48 hours of meeting inclusion criteria.
1. Age \> 18 years
2. Presence of all of the following conditions for \< 48 hours:
i. PaO2/FiO2 \< 150 with PEEP \>/= 8 cm H2O OR, if ABG not available, SaO2/FiO2 ratio that is equivalent to a PaO2/FiO2 \< 150 with PEEP \>/= 8 cm H2O , and a confirmatory SaO2/FiO2 ratio that is again equivalent 1-6 hours later
ii. Bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules.
iii. Respiratory failure not fully explained by cardiac failure or fluid overload; need objective assessment (e.g., echocardiography) to exclude hydrostatic edema if no risk factor present.
Patients must be enrolled within 48 hours of meeting inclusion criteria.
Gender
All
Gender Based
false
Keywords
ARDS
neuromuscular blocker
cisatracurium
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02509078
Org Class
Other
Org Full Name
Massachusetts General Hospital
Org Study Id
PETAL01ROSE
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Reevaluation Of Systemic Early Neuromuscular Blockade
Primary Outcomes
Outcome Description
The percentage of subjects alive at study day 90. Those subjects discharged home prior to day 90 were counted as alive at day 90.
Outcome Measure
Hospital Mortality to Day 90
Outcome Time Frame
90 days after randomization
Secondary Ids
Secondary Id
1U01HL123009-01
Secondary Outcomes
Outcome Description
Ventilator-free days is defined to be 28 days minus the duration of mechanical ventilation through day 28. Participants who do not survive to day 28 are assigned zero ventilator-free days.
Outcome Time Frame
28 days after randomization
Outcome Measure
Mean Ventilator Free Days to Day 28
Outcome Description
SOFA (Sepsis-related Organ Failure Assessment) was used to determine criteria for an organ failure free day. Scores were based on four of the six SOFA organ categories: Coagulation, Liver, Cardiovascular, and Renal. Each category was scored 0-4; 0 being normal functioning and 4 being the most abnormal. A patient was considered failure free on each day alive with SOFA scores below 2 for all four organ systems.
Ref: Vincent, J.L., et al., The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med, 1996. 22(7): p. 707-10.
Ref: Vincent, J.L., et al., The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med, 1996. 22(7): p. 707-10.
Outcome Time Frame
28 days after randomization
Outcome Measure
Mean Organ Failure Free Days to Day 28
Outcome Description
ICU free days is defined as the number of days between randomization and day 28 in which the patient is in the ICU (for any part of a day).
Outcome Time Frame
28 days after randomization
Outcome Measure
ICU Free Days to Day 28
Outcome Description
Hospital free days are days alive post hospital discharge through day 28. Patients who die on or prior to day 28 are assigned zero hospital free days.
Outcome Time Frame
28 days after randomization
Outcome Measure
Mean Hospital Free Days to Days 28
Outcome Description
Assesses whether individual can living independently and assess a range of common functional activities, from walking and toileting to managing money and cooking meals. Data is a pooled estimates from patient survey and proxy survey. The total score is rated from 0 to 10 (MCID=1; 1 point=1 ADL); a higher score indicates having more difficulties in daily activities.
Outcome Time Frame
3 months after randomization
Outcome Measure
Katz Activities of Daily Living (ADL)/Lawton Instrumental Activities Of Daily Living Scale (IADL)
Outcome Description
Using a standardized scale, do health reasons limit the person's ability to enjoy their life? Pooled estimates from patient survey and proxy survey were used. Utility index was computed from a lookup table according to EQ-5D-5L response profiles; utility index ranges from -0.11 to 1.00 (higher scores are better; 1.00 is perfect health), minimal clinically important difference (MCID) is 0.07
Outcome Time Frame
3 months after randomization
Outcome Measure
EuroQol (EQ-5D-5L): Health Related Quality of Life
Outcome Description
Does the patient have symptoms of anxiety and stress from their ICU stay? PTSS-14 is only asked at month 6 and month 12 in patient survey; total score is rated from 14 to 98 and a higher score indicates having more post-traumatic stress syndrome related symptoms. Participants with scores greater than or equal to 45 were reported.
Outcome Time Frame
6 months after randomization
Outcome Measure
PTSS-14: Post-traumatic Stress-like Symptoms Scores >/= 45
Outcome Description
How clearly can patient think and recall things? MoCA-Blind is only asked in patient survey; total score is rated from 0 to 30 and a higher score indicates better cognitive performance. Normal range: 26 or greater.
Outcome Time Frame
3 months after randomization
Outcome Measure
MoCA-Blind: Montreal Cognitive Assessment
Outcome Description
Assesses whether individual can living independently and assess a range of common functional activities, from walking and toileting to managing money and cooking meals. Data is a pooled estimates from patient survey and proxy survey. The total score is rated from 0 to 10 (MCID=1; 1 point=1 ADL); a higher score indicates having more difficulties in daily activities.
Outcome Time Frame
6 months after randomization
Outcome Measure
Katz Activities of Daily Living (ADL)/Lawton Instrumental Activities Of Daily Living Scale (IADL)
Outcome Description
Assesses whether individual can living independently and assess a range of common functional activities, from walking and toileting to managing money and cooking meals. Data is a pooled estimates from patient survey and proxy survey. The total score is rated from 0 to 10 (MCID=1; 1 point=1 ADL); a higher score indicates having more difficulties in daily activities.
Outcome Time Frame
12 months after randomization
Outcome Measure
Katz Activities of Daily Living (ADL)/Lawton Instrumental Activities Of Daily Living Scale (IADL)
Outcome Description
Using a standardized scale, do health reasons limit the person's ability to enjoy their life? Pooled estimates from patient survey and proxy survey were used. Utility index was computed from a lookup table according to EQ-5D-5L response profiles; utility index ranges from -0.11 to 1.00 (higher scores are better; 1.00 is perfect health), minimal clinically important difference (MCID) is 0.07
Outcome Time Frame
6 months after randomization
Outcome Measure
EuroQol (EQ-5D-5L): Health Related Quality of Life
Outcome Description
Using a standardized scale, do health reasons limit the person's ability to enjoy their life? Pooled estimates from patient survey and proxy survey were used. Utility index was computed from a lookup table according to EQ-5D-5L response profiles; utility index ranges from -0.11 to 1.00 (higher scores are better; 1.00 is perfect health), minimal clinically important difference (MCID) is 0.07
Outcome Time Frame
12 months after randomization
Outcome Measure
EuroQol (EQ-5D-5L): Health Related Quality of Life
Outcome Description
How clearly can patient think and recall things? MoCA-Blind is only asked in patient survey; total score is rated from 0 to 30 and a higher score indicates better cognitive performance. Normal range:
26 or greater.
26 or greater.
Outcome Time Frame
6 months after randomization
Outcome Measure
MoCA-Blind: Montreal Cognitive Assessment
Outcome Description
How clearly can patient think and recall things? MoCA-Blind is only asked in patient survey; total score is rated from 0 to 30 and a higher score indicates better cognitive performance. Normal range:
26 or greater.
26 or greater.
Outcome Time Frame
12 months after randomization
Outcome Measure
MoCA-Blind: Montreal Cognitive Assessment
Outcome Description
Does the patient have symptoms of anxiety and stress from their ICU stay? PTSS-14 is only asked at month 6 and month 12 in patient survey; total score is rated from 14 to 98 and a higher score indicates having more post-traumatic stress syndrome related symptoms. Participants with scores greater than or equal to 45 were reported.
Outcome Time Frame
12 months after randomization
Outcome Measure
PTSS-14: Post-traumatic Stress-like Symptoms Scores >/= 45
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Michelle Gong
Investigator Email
mgong@montefiore.org
Investigator Phone
718-920-5464
Categories Mesh Debug
Lung & Chest Cancers --- LUNG DISEASES
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
MeSH Terms
RESPIRATORY DISTRESS SYNDROME
LUNG DISEASES
RESPIRATORY TRACT DISEASES
RESPIRATION DISORDERS
CISATRACURIUM