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This is a randomized, open, multicenter, pragmatic, adaptive clinical trial with intention-to-treat analysis. The study will compare two weaning strategies from mechanical ventilation in critically ill patients admitted to intensive care units, with more than 72 hours of mechanical ventilation and with a successful spontaneous breathing trial on T-piece. Immediately after a successful spontaneous breathing trial, eligible patients will be randomized into 2 groups that will be treated according to one of the following interventions:
Adaptive design for sample size. The study will include up to a maximum of 4.000 patients. First interim analysis will be performed after complete data is available for the first 500 eligible patients. The Bayesian logistic regression model will be adjusted to provide posterior probabilities that will be compared with threshold values to evaluate stopping decisions. Extensive simulations were conducted to develop and understand adaptive design performance, interim analysis timing, and decision criteria. The trial may be stopped early for efficacy or futility. Secondary outcomes will be analyzed with a gatekeeping procedure to preserve overall type I error at 0.05. Thus, the assessment of statistical significance of secondary outcomes will be performed only if the preceding outcome in the hierarchy met the threshold for statistical significance. No adjustment for multiple comparisons will be applied for analyses of tertiary outcomes and subgroups. Thus, these results should be interpreted as exploratory. Secondary outcomes tested in hierarchical order will be: (1) Mechanical ventilation free days within 28 days; (2) Hospital free days within 28 days; (3) Mortality within 28 days.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| One-hour positive pressure ventilation | Experimental |
| |
| Immediate extubation | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| One-hour positive pressure ventilation | Other | As soon as the success of the spontaneous breathing trial is confirmed, the patient is submitted to mechanical ventilation for 1 hour using the previous ventilatory parameters and, afterwards, extubated. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Extubation Failure Within 7 Days | Extubation failure is defined as a composite endpoint of reintubation or death within 7 days after randomization. | 7 days (from randomization through Day 7 after randomization) |
| Measure | Description | Time Frame |
|---|---|---|
| Ventilator-Free Days Through Day 28 | Ventilator-free days are defined as the number of days alive and free from invasive mechanical ventilation from randomization through Day 28 after randomization. If a patient dies before day 28, the ventilator-free days will be counted as zero. If a patient is reintubated and returns to mechanical ventilation and later is extubated again and remains in unassisted breathing until day 28, the ventilator-free days will be counted from the end of the last period of assisted breathing until day 28. An invasive mechanical ventilation period of less than 24 hours for surgical purposes will count as 1 ventilator-free day. Patients discharged from the hospital in unassisted breathing before 28 days will be considered alive and free from mechanical ventilation for the remaining days up to 28 days. Patients transferred to another hospital or healthcare unit will be followed up until day 28 to assess this outcome. |
| Measure | Description | Time Frame |
|---|---|---|
| Ventilatory Support-Free Days Through Day 28 | Ventilatory support-free days are defined as the number of days alive and free from any ventilatory support (invasive or noninvasive) from randomization through day 28. Any use of invasive mechanical ventilation for any duration during a calendar day will count as 1 day with ventilatory support (i.e., not free). Use of noninvasive ventilatory support (noninvasive ventilation or high-flow nasal cannula) for ≥6 hours in any calendar day will count as 1 day with ventilatory support. Participants who die before day 28 will be assigned 0 ventilatory support-free days. If reintubation occurs and the participant later achieves unassisted spontaneous breathing again, ventilatory support-free days will be counted from the end of the last assisted-breathing period through day 28, provided the participant remains alive and free from ventilatory support. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Aline B Pereira | Contact | +55 (47) 99181-8400 | linibp@hotmail.com |
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| ID | Term |
|---|---|
| D011175 | Positive-Pressure Respiration |
| ID | Term |
|---|---|
| D012121 | Respiration, Artificial |
| D058109 | Airway Management |
| D013812 | Therapeutics |
| D012138 | Respiratory Therapy |
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| Immediate extubation | Other | The patient is extubated immediately after the success of the spontaneous breathing trial. |
|
| 28 days (from randomization through Day 28 after randomization) |
| Hospital-Free Days Through Day 28 | Hospital-free days are defined as the number of days alive and out of the hospital from randomization through Day 28 after randomization. If a patient dies before day 28, the hospital-free days will be counted as zero. Patients discharged from the hospital in unassisted breathing before 28 days will be considered alive and free from hospital for the remaining days up to 28 days. Patients transferred to another hospital or healthcare unit will be followed through day 28 to ascertain this outcome. | 28 days (from randomization through Day 28 after randomization) |
| Number of Participants Who Died Within 28 Days | All-cause mortality from randomization through day 28 | 28 days (from randomization through Day 28 after randomization) |
| 28 days (from randomization through Day 28 after randomization) |
| Number of Participants With Extubation Failure Within 2 Days | Extubation failure is defined as a composite endpoint of reintubation or death within 2 days after randomization | 2 days (from randomization through Day 2 after randomization) |
| Number of Participants With Death or Reintubation Within 28 Days | Composite endpoint of reintubation or death within 28 days after randomization | 28 days (from randomization through Day 28 after randomization) |
| Intensive Care Unit-Free Days Through Day 28 | ICU-free days are defined as the number of days alive and out of the intensive care unit from randomization through day 28. If a patient dies before day 28, the ICU-free days will be counted as zero. Patients discharged from the hospital in unassisted breathing before 28 days will be considered as alive and free from ICU for the remaining days up to 28 days. Patients transferred to another hospital or healthcare unit will be followed up until day 28 to assess this outcome. | 28 days (from randomization through Day 28 after randomization) |
| Number of Participants Who Died in the Intensive Care Unit | All-cause mortality occurring from randomization until ICU discharge (death before ICU discharge). | From randomization to ICU discharge, up to 90 days |
| Number of Participants Who Died in the Hospital | All-cause mortality occurring from randomization until hospital discharge (death before hospital discharge) | From randomization to hospital discharge, up to 90 days |