Recruiting NA Respiratory Insufficiency

New treatment option for Respiratory Insufficiency

Official title Platform of Randomized Adaptive Clinical Trials in Critical Illness

ClinicalTrials.gov ID: NCT05440851

What this study is testing

What is Early Cohort corticosteroid dose?

Early Cohort corticosteroid dose is an investigational medicine, given as an once-daily inhaled treatment, being studied as a potential treatment for respiratory insufficiency.

Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.

What it's testing: PRACTICAL is a randomized multifactorial adaptive platform trial for acute hypoxemic respiratory failure (AHRF). This platform trial will evaluate novel interventions for patients with AHRF across a range of severity states (i.e., not intubated, intubated with lower or higher respiratory system elastance, requiring extracorporeal life support) and across a range of investigational phases (i.e., preliminary mechanistic trials, full-scale clinical trials).

Which group you join is decided by chance.

A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.

Who can take part

Ages 18 and older

You may be able to join if

PRACTICAL Platform
Acute hypoxemic respiratory failure meeting all of the following criteria;
New or worsening respiratory symptoms developing within 2 weeks prior to the onset of need for oxygen or respiratory support
Receiving any of the following types of oxygen or respiratory support for at least 4 hours prior to the time of randomization; supplemental oxygen at...
Minimum FiO2 ≥ 0.40 (for venturi mask, high flow nasal cannula, or invasive or non-invasive ventilation) or oxygen flow rate ≥10 L/min on face mask...

You likely can't join if

Extubation is planned or anticipated on the day of screening
ICU discharged is planned or anticipated on the day of screening
If the patient is moribund and deemed unlikely to survive 24 hours (as determined by the clinical team)
If the patient is being transitioned to a fully palliative philosophy of care EXPAND-ECLS Domain Inclusion Criteria:
Receiving invasive Endotracheal mechanical ventilation for ≤ 72 hours.5 days
Early Moderate-severe hypoxemic respiratory failure with a PaO2/FiO2≤150200 mmHg for at least 6 hours EXPAND-ECLS Domain Exclusion Criteria:

See the full eligibility criteria

Who can join

PRACTICAL Platform
Acute hypoxemic respiratory failure meeting all of the following criteria;
New or worsening respiratory symptoms developing within 2 weeks prior to the onset of need for oxygen or respiratory support
Receiving any of the following types of oxygen or respiratory support for at least 4 hours prior to the time of randomization; supplemental oxygen at 10 L/min or higher, high flow nasal oxygen (at any flow rate)...
Minimum FiO2 ≥ 0.40 (for venturi mask, high flow nasal cannula, or invasive or non-invasive ventilation) or oxygen flow rate ≥10 L/min on face mask for at least 4 hours at the time of evaluation for eligibility unless...
Age ≥ 18 years
Hypoxemia not primarily attributable to acute heart failure, fluid overload, or pulmonary embolism (PE) PRACTICAL Platform

What rules you out

Extubation is planned or anticipated on the day of screening
ICU discharged is planned or anticipated on the day of screening
If the patient is moribund and deemed unlikely to survive 24 hours (as determined by the clinical team)
If the patient is being transitioned to a fully palliative philosophy of care EXPAND-ECLS Domain Inclusion Criteria:
Receiving invasive Endotracheal mechanical ventilation for ≤ 72 hours.5 days
Early Moderate-severe hypoxemic respiratory failure with a PaO2/FiO2≤150200 mmHg for at least 6 hours EXPAND-ECLS Domain Exclusion Criteria:
Patients over 70 years of age.
Currently receiving any form of ECLS (e.g., Venovenous, venoarterial, or hybrid configuration).
Chronic hypercapnic respiratory failure defined as PaCO2 \> 60 mmHg in the outpatient setting.
Home mechanical ventilation (non-invasive ventilation or via tracheotomy) except for CPAP/BiPAP used solely for sleep-disordered breathing.
Actual body weight exceeding 1 kg per centimeter of height.
More than 48 hours have passed since meeting inclusion criteria.
Severe hypoxemia with PaO2/FiO2 \ 6 hours at time of screening.
Severe hypercapnic respiratory failure with pH \ 60 mmHg for \> 6 hours at time of screening.
Expected mechanical ventilation duration \< 48 hours at time of screening.
Confirmed diffuse alveolar hemorrhage from vasculitis.
Contraindications to limited anticoagulation (e.g., active GI bleeding, bleeding diathesis).
Previous hypersensitivity/anaphylactic reaction to heparin or heparin-induced thrombocytopenia
Neurologic conditions at risk for or undergoing treatment for intracranial hypertension
Underlying illness with life expectancy \< 1 year
Pregnancy (due to unknown effects of PaCO2 changes on placental blood flow)
Respiratory failure known or suspected to be caused by COVID-19. IMV Domain Inclusion Criteria:
Intubated patients, not on ECLS, with low normalized respiratory elastance (\<2.5 cm H2O/(ml/kg predicted body weight)) at the time of eligibility assessment OR
Intubated patients, not on ECLS, with high normalized respiratory system elastance (≥2.5 cm H2O/(ml/kg predicted body weight)) at the time of eligibility assessment OR
FOR STUDY SITES PARTICIPATING IN THE LDPVS INTERVENTION: Patient is on ECLS at the time of eligibility assessment. Note: Patients in this state are only eligible for the LPV or LDPVS intervention
FOR STUDY SITES PARTICPATING IN THE EIT INTERVENTION: PaO2/FiO2 (if available) \< 200 mm Hg at randomization. If PaO2/FiO2 has not been measured, SpO2 = 97% on FiO2 =60%. IMV Domain Exclusion Criteria:
PaO2/FiO2 \>300 mm Hg or (S/F \>250, if PaO2/FiO2 has not been measured) at the time of randomization
Chronic hypercapnic respiratory failure defined as PaCO2\>60mmHg in the outpatient setting
Home mechanical ventilation (non-invasive ventilation or via tracheotomy), not including nocturnal CPAP applied by nasal or face mask or home tracheotomy if not ventilated
Severe hypoxemia with PaO2/FiO2\ 6 consecutive hours at the time of randomization
Severe hypercapnic respiratory failure with pH\ 60mmHg for \>6 consecutive hours at the time of randomization
Anticipated duration of mechanical ventilation is \<48 hours from the time of screening
Duration of mechanical ventilation during current ICU admission is \>72 hours
Previously diagnosed neuromuscular disorder
Current diagnosis of severe acute brain injury (e.g. ischemic or hemorrhagic stroke, traumatic brain injury) with Glasgow Coma Scale ≤ 8
Baseline weight prior to or at hospital admission less than 35 kilograms
Receiving extracorporeal life support without continuous invasive mechanical ventilatory support CORT-E2 Domain Early Cohort Inclusion Criteria
Within 72 hours of admission to an ICU
New unilateral or bilateral airspace disease CORT-E2 Domain Early Domain Exclusion Criteria
Receiving only low flow oxygen therapy less than or equal to 15L/min
Corticosteroid use during the 14 days prior to screening
Existing indication for corticosteroids
High suspicion for/or confirmed COVID infection
Acute traumatic brain injury during the index hospital admission
Allergy to dexamethasone CORT-E2 Domain Extended Cohort Inclusion Criteria
Are admitted to an ICU
Have already received 10 days of corticosteroid specifically for acute respiratory failure, this will include patients: (a) assigned by chance to corticosteroid arm in Early Cohort, (b) patients with COVID receiving...
Ongoing AHRF requiring HFNC, NIV (continuous positive airway pressure [CPAP] or bilevel) or invasive ventilation CORT-E2 Domain Extended Cohort Exclusion Criteria
An alternate indication for ongoing corticosteroids
Acute traumatic brain injury this hospital admission FLUDRO Domain Inclusion Criteria 1. Within 72 hours of admission to an ICU FLUDRO Domain Exclusion Criteria
Known hypersensitivity to fludrocortisone
An inability to receive fludrocortisone due to lack of enteral access
An indication to prescribe fludrocortisone for a reason that is unrelated to a current episode of pneumonia or acute respiratory failure, such as Addison's disease
Belief of the treating clinical team that study participation would not be in the best interest of the patient FAST-3 Domain Inclusion Criteria (must meet all 3 of the following)
Patient is in a PRACTICAL eligible platform state and requires advanced respiratory support (ARS) defined as one of the following: a. Invasive mechanical ventilation with FiO2 \> 40% b. Non-Invasive Ventilation (\> 4...
PaO2/FiO2 \< 300 mm Hg or SpO2/FiO2 \< 315 (if PaO2/FiO2 unavailable due to lack of arterial blood gas at the time of screening). For SpO2/FiO2, criteria are SpO2 ≤ 97% on FiO2 ≥ 40% on both of the 2 hours immediately...
Patient commenced advanced respiratory support \< 48 hours prior to randomization. FAST-3 Domain Exclusion Criteria
Patient commenced advanced respiratory support \> 48 hours to time of randomization.
Known history of severe chronic pulmonary disease e.g., pre-infection requirement for home oxygen therapy or presence of chronic hypercapnia (PaCO2 \> 60 mmHg); mild - moderate disease is still eligible in the absence...
Currently enrolled in another trial studying investigational anti-inflammatory therapy, excluding established treatments used in clinical practice such as corticosteroids.
Known allergy to furosemide or sulfonamide drugs. If the patient is allergic to sulfonamide drugs but has received in the past or is currently receiving furosemide without incident, they can be enrolled since...
Patients with severe AHRF who have an underlying immunocompromised condition
Within 48 hours of fulfilling the AHRF inclusion criteria as well as PaO2/FiO2 \<300 or a SaO2/FiO2 \< 315 on non-invasive respiratory support (venturi mask, non-invasive ventilation or high flow nasal oxygen as per the...
Any patients requiring long term (\>30 days) corticosteroids (\>20 mg/day),
Any patients receiving non-corticosteroid immunosuppressive medications within the prior 3 months,
Acquired or inherited immunodeficiency syndrome,
Recipients of solid organ transplant,
Active hematologic malignancy (diagnosis or receiving treatment within prior 6 months),
Active solid tumor (diagnosis or receiving treatment within the prior 6 months) or
Any patients who have undergone allogeneic or autologous hematopoietic cell transplant in the prior 6 months (HCT). ESCAPE Domain Exclusion Criteria
Patients whom are deemed palliative. WAVEFORM Domain Inclusion Criteria 1\. Patient is intubated at the time of eligibility assessment. WAVEFORM Domain Exclusion Criteria
PaO2/FiO2 \>300 mm Hg or (S/F \>250, if PaO2/FiO2 has not been measured) at the time of eligibility assessment.
Duration of mechanical ventilation during current ICU admission is ≥72 hours.
Receiving ECLS without continuous invasive mechanical ventilatory support. IMV-ECLS Domain Inclusion Criteria 1\. Patients with AHRF (as defined in platform inclusion criteria #1 above) who have been consented for...
Patients receiving invasive mechanical ventilation for AHRF as defined by the PRACTICAL platform trial criteria above.
Within 7 calendar days of intubation IMPROV Domain Exclusion Criteria
Patient is expected to be liberated from mechanical ventilation within 24 hours
Known or suspected chronic hypercapnic respiratory failure defined as PaCO2\>60mmHg in the outpatient setting
Home mechanical ventilation (non-invasive ventilation or via tracheotomy), not including nocturnal CPAP applied by nasal or face mask or home tracheotomy if not ventilated
Known pneumothorax or pneumomediastinum without chest tube placement sustained during current ICU admission\ (re-confirm immediately prior to randomization)
Patient is admitted primarily for acute brain injury (stroke, traumatic brain injury, etc.)
Previously diagnosed chronic neuromuscular disorder
Patient has an implantable cardiac defibrillator or pacemaker
Planned to be transferred to another hospital before ICU discharge
Already receiving a regimen of inspiratory muscle training using external resistive device or diaphragm neurostimulation

The study team makes the final eligibility decision.

Where it's taking place

Tucson, Arizona, United States
Los Angeles, California, United States
San Diego, California, United States
San Francisco, California, United States
Aurora, Colorado, United States
Lexington, Kentucky, United States
Baltimore, Maryland, United States
Ann Arbor, Michigan, United States
St Louis, Missouri, United States
Omaha, Nebraska, United States
New York, New York, United States
Winston-Salem, North Carolina, United States
Cincinnati, Ohio, United States
Cleveland, Ohio, United States
Portland, Oregon, United States
Philadelphia, Pennsylvania, United States
Pittsburgh, Pennsylvania, United States
Providence, Rhode Island, United States
Charleston, South Carolina, United States
Nashville, Tennessee, United States

+ 50 more site(s).

Compensation & support

Compensation mentioned.

ClinicalTrials.gov doesn't provide a reliable structured field for payment or travel support - confirm details with the study team.

Questions & answers

Do participants get paid in this trial?

This study's listing includes signals that participants may be compensated or receive a stipend. Amounts vary and are set by the study team - confirm the details with them.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Tucson, Arizona, United States; Los Angeles, California, United States; San Diego, California, United States; San Francisco, California, United States; Aurora, Colorado, United States; Lexington, Kentucky, United States and 64 more location(s). Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.