Acute Respiratory Distress SyndromeNCT04744298
Identification and Treatment of Hypoxemic Respiratory Failure and ARDS With Protection, Paralysis, and Proning Pathway
A study testing TheraPPP in people with Acute Respiratory Distress Syndrome and Hypoxemic Respiratory Failure, run by University of Calgary at 17 sites in Canada.
Trial summary
Treatment of patients with Hypoxemic respiratory failure (HRF) and Acute Respiratory Distress Syndrome (ARDS) is complex. Therapies that have been shown to save the lives of patients with HRF and ARDS are available but they are not always provided. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Distress Syndrome, Hypoxemic Respiratory Failure, ARDS, Human
- What is being tested?
- TheraPPP
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19,916 participants
- Where
- 17 sitesCanada
- Study dates
- 1 Apr 2021to 31 Dec 2026
- Phase
- Interventional
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Admitted to the one of the 17 adult Intensive Care Units in Alberta
- Invasively mechanically ventilated
Who cannot join
- none
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
Canada17 sites
Peter Lougheed Centre (PLC)
Calgary, Alberta, T1Y 6J4
Foothills Hospital Intensive Care Unit
Calgary, Alberta, T2N 2T9
Foothills Medical Center Cardiovascular ICU
Calgary, Alberta, T2N 2T9
Rockyview General Hospital
Calgary, Alberta, T2V 1P9
South Health Campus
Calgary, Alberta, T3M 1M4
Royal Alexandra Hospital
Edmonton, Alberta, T5H 3V9
Misericordia Community Hospital
Edmonton, Alberta, T5R 4H5
Mazankowski Alberta Heart Institute
Edmonton, Alberta, T6G 2B7
University of Alberta Hospital General Systems ICU
Edmonton, Alberta, T6G 2B7
University of Alberta Hospital Neurosciences Intensive Care Unit
Edmonton, Alberta, T6G 2B7
Grey Nuns Community Hospital
Edmonton, Alberta, T6L 5X8
Northern Lights Regional Health Centre
Fort McMurray, Alberta, T9H 1P2
Queen Elizabeth II Hospital
Grande Prairie, Alberta, T8V 2E8
Chinook Regional Hospital
Lethbridge, Alberta, T1J 1W5
Medicine Hat Regional Hospital
Medicine Hat, Alberta, T1A 4H6
Red Deer Regional Hospital Centre
Red Deer, Alberta, T4N 4E7
Sturgeon Community Hospital
St. Albert, Alberta, T8N 6C4
About this study
Official title: Identification and Treatment of Hypoxemic Respiratory Failure (HRF) and ARDS With Protection, Paralysis, and Proning: TheraPPP Study
Treatment of patients with Hypoxemic respiratory failure (HRF) and Acute Respiratory Distress Syndrome (ARDS) is complex. Therapies that have been shown to save the lives of patients with HRF and ARDS are available but they are not always provided. To reduce practice variation and improve adherence to evidence-informed therapies, the investigators developed the Treatment of Hypoxemic Respiratory Failure and ARDS with Protection, Paralysis, and Proning (TheraPPP) Pathway.
The overall objective of TheraPPP Pathway is to improve the quality of care for patients with HRF. Implementation of the pathway across Alberta will test the effectiveness and implementation of the TheraPPP Pathway.
Read the detailed description
Hypoxemic respiratory failure (HRF) and ARDS are common conditions among patients admitted to the Intensive care unit (ICU). Treatment of these patients is complex. Evidence based therapies that can improve survival exist; however, implementation is extremely inconsistent. As a potential solution to this problem, the investigators developed the Treatment of Hypoxemic Respiratory Failure (HRF) and ARDS with Protection, Paralysis, and Proning (TheraPPP) Pathway to reduce practice variation and improve adherence to evidence-informed therapy.
The TheraPPP pathway is a comprehensive evidence-based, stakeholder-informed pathway for the diagnosis and management of HRF. The overall objective of the pathway is to improve the quality of care for patients with HRF. The specific objectives are to evaluate:
- Effectiveness of the pathway. A cost-effectiveness analysis is a secondary objective.
- Implementation of the pathway by conducting a process evaluation which will assess fidelity of the delivered interventions and clinician perceptions about the acceptability of the pathway.
Mechanically ventilated patients admitted to any one of 17 adult ICUs in Alberta will receive the intervention. One ICU (Calgary) is the setting for a pilot study (NCT04070053).
For data analysis, the investigators will use chart abstraction to quantitatively assess the fidelity of the delivered intervention, and surveys and focus groups to qualitatively assess clinician perceptions about the acceptability of the pathway. Fidelity of the intervention will be tracked using process of care indicators that reflect the five key steps of the pathway.
- Being tested
- TheraPPP
- Medical subject headings
- Respiratory Distress Syndrome, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TheraPPPOther
TheraPPP Steps:
Step 1. All mechanically ventilated patients will have a height measured and documented. Step 2. Screening for HRF. Step 3. Initiate Lung Protective Ventilation (LPV). Step 4. Paralysis. Step 5. Prone Positioning.
| Study group | Role | What they receive |
|---|---|---|
| TheraPPP Pathway | Experimental | The investigators will perform an effectiveness-implementation hybrid study design (type 1) to evaluate the effectiveness and implementation of the TheraPPP pathway.
All mechanically ventilated patients admitted to the ICU will enter the pathway. To evaluate effectiveness the investigators will collect patient data for approximately 29 months. To assess acceptability of the pathway the investigators will conduct a survey and focus groups to clinicians who used the Pathway. Receives: Other: TheraPPP |
What is being measured
The primary outcome is the main question the study is designed to answer.
EFFECTIVENESS (primary clinical outcome) 28-day ventilator free days
A composite outcome of survival and days spent not ventilated over the first 28 days
Measured: 4 months (after the study post-intervention period)
IMPLEMENTATION (primary fidelity outcome) Composite Fidelity Score
The composite fidelity score is measured daily for each patient. It is scored out of 5 and awards 1 point for each fidelity indicator (listed below) that investigators are able to measure:
- If ventilated, is a height measured (step 1)
- If arterial to inspired oxygen ratio (PaO2:FiO2 ratio or PF ratio) ≤300, is the medial tidal volume ≤8mL/kg (step 2)
- If PF ratio ≤300, is a plateau pressure measured (step 3)
- IF patient has HRF and PF ratio ≤150, was neuromuscular blockade used in that 24 hour period (step 4)
- If the patient has HRF and PF ratio ≤150 and FiO2 ≥0.6, did the patient receive prone ventilation (step 5)
Measured: 4 months (after the study post-intervention period)
ECONOMIC (primary economic outcome) Cost per ventilator free day saved
Cost per ventilator free day saved from the perspective of the health care system over the index hospitalization period
Measured: 4 months (after the study post-intervention period)
Secondary outcomes (22)
28-day and hospital survival
Number of patients who die in the ICU, hospital, and at or before 28-day hospital censored at 90 days
Measured: 90 days
Ventilator duration
The number of ventilated days. If a patient is invasively mechanically ventilated via endotracheal tube or tracheostomy for any period of time in a 24 hour period (0000-2359) this is considered a ventilated day. A ventilated day is the component of VFDs that reflects duration of ventilation.
Measured: 4 months (after the study post-intervention period)
Driving Pressure
Calculated on patients ventilated with PF ratio (partial pressures of oxygen (paO2) / fraction of inspired oxygen (FiO2) ≤ 300 on a controlled mode as plateau pressure - positive end expiratory pressure (PEEP).
Measured: 4 months (after the study post-intervention period)
Mechanical Power
Calculated on patients ventilated with PF ratio ≤ 300 on a controlled mode using the formula Power = 0.098*respiratory rate•(tidal volume/1000)*(Peak Pressure - (0.5 • Driving Pressure)).
Measured: 4 months (after the study post-intervention period)
ICU and hospital length of stay
The number of days that patients stay in the ICU and in hospital
Measured: 4 months (after the study post-intervention period)
Proportion of patients receiving rescue therapies specifically Extracorporeal Life Support (ECLS)
The proportion of patients receiving rescue therapies including ECLS
Measured: 4 months (after the study post-intervention period)
The proportion of patients ventilated with a height measured
Total number of ventilated patients for with a height measured divided by the total number of patients ventilated
Measured: 4 months (after the study post-intervention period)
Proportion of patient days with PF ratio ≤300 with a tidal volume ≤8mL/kg
The total number of patient days with arterial to inspired oxygen ratio(PaO2:FiO2 ratio or PF ratio) ≤300 with a tidal volume ≤8 mL/kg divided by the total number of of patient days with arterial to inspired oxygen ratio (PaO2:FiO2 ratio or PF ratio) ≤300
Measured: 4 months (after the study post-intervention period)
Proportion of patient days with PF ratio ≤300 with a plateau pressure measured
The total number of patient days with PF ratio ≤300 with a plateau pressure measured divided by the total number of patient days with PF ratio ≤300
Measured: 4 months (after the study post-intervention period)
Proportion of patient days with HRF and PF ratio ≤150 who receive neuromuscular blockade
The number of patient days with HRF and PF ratio ≤150 who receive neuromuscular blockade divided by the number of patient days with HRF and PF ratio ≤150
Measured: 4 months (after the study post-intervention period)
Proportion of patient days with HRF and PF ratio ≤150 and FiO2 ≥0.6 receiving prone ventilation
The number of patient days with HRF and PF ratio ≤150 and FiO2 ≥0.6 receiving prone ventilation divided by the number of patient days with HRF and PF ratio ≤150 and FiO2 ≥0.6
Measured: 4 months (after the study post-intervention period)
Theoretical Framework of Acceptability - Composite Acceptability Score
Pathway acceptability is measured using the Theoretical Framework of Acceptability (TFA). The primary outcome for acceptability is a composite score of the proportion of seven TFA constructs [(1) affective attitude (2) burden (3) ethicality (4) intervention coherence (5) opportunity costs (6) perceived effectiveness (7) self-efficacy] graded with a median score of 4 or above from a 5-point Likert scale, in which 1 indicates strong disagreement (and lower acceptability) and 5 indicates strong agreement (and higher acceptability).
Measured: 4 months (after the study post-intervention period)
Theoretical Framework of Acceptability - Opportunity costs construct
Benefits or costs to the participant for using the pathway graded on a 5-point Likert scale in which 1 indicates strong disagreement (and lower acceptability) and 5 indicates strong agreement (and higher acceptability), Median (IQR)
Measured: 4 months (after the study post-intervention period)
Theoretical Framework of Acceptability - Perceived effectiveness construct
The extent to which the intervention is perceived as likely to achieve its purpose graded graded on a 5-point Likert scale in which 1 indicates strong disagreement (and lower acceptability) and 5 indicates strong agreement (and higher acceptability), Median (IQR)
Measured: 4 months (after the study post-intervention period)
Theoretical Framework of Acceptability - Affective attitude construct
How an individual feels about the intervention graded on a 5-point Likert scale in which 1 indicates strong disagreement (and lower acceptability) and 5 indicates strong agreement (and higher acceptability), Median (IQR)
Measured: 4 months (after the study post-intervention period)
Theoretical Framework of Acceptability - Burden construct
The perceived amount of effort that is required to participate in the intervention graded on a 5-point Likert scale in which 1 indicates strong disagreement (and lower acceptability) and 5 indicates strong agreement (and higher acceptability), Median (IQR)
Measured: 4 months (after the study post-intervention period)
Theoretical Framework of Acceptability - Ethicality construct
The extent to which the intervention has a good fit with an individual's value graded on a 5-point Likert scale in which 1 indicates strong disagreement (and lower acceptability) and 5 indicates strong agreement (and higher acceptability), Median (IQR)
Measured: 4 months (after the study post-intervention period)
Theoretical Framework of Acceptability - Self efficacy construct
The participant's confidence that they can perform the behavior(s) required to participate in the intervention graded on a 5-point Likert scale in which 1 indicates strong disagreement (and lower acceptability) and 5 indicates strong agreement (and higher acceptability), Median (IQR)
Measured: 4 months (after the study post-intervention period)
Theoretical Framework of Acceptability - Intervention coherence construct
The extent to which the participant understands the invention and how it works graded on a 5-point Likert scale in which 1 indicates strong disagreement (and lower acceptability) and indicates strong agreement (and higher acceptability), Median (IQR)
Measured: 4 months (after the study post-intervention period)
Total cost: ICU admission
Total cost for the ICU admission
Measured: 4 months (after the study post-intervention period)
Total cost: Index hospitalization
Total cost for the index hospitalization
Measured: 4 months (after the study post-intervention period)
Cost per quality adjusted life year (QALY)
Cost per quality adjusted life year (QALY) from the health care system perspective over the patient's lifetime
Measured: 4 months (after the study post-intervention period)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2021
- Study start1 Apr 2021
- Primary completion20 Mar 2024
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The study uses an effectiveness-implementation hybrid design (type 1). Phase 1 will evaluate effectiveness and Phase 2 will assess the implementation of the pathway. Implementation will occur via a pragmatic registry-based stepped wedge cluster randomization of ICUs. The unit of randomization will be a cluster of 2 ICUs. The intervention will be implemented into 1 cluster every 2 months. Once implemented, the cluster will continue to receive it for the remainder of the study. Effectiveness: There will be a 10-month baseline data collection period at the beginning of the study. The total study duration will be 29 months (Estimated18816 mechanically ventilated patients including 2688 in the ARDS subgroup). The comparison (control) therapy will be usual management assessed in the baseline period. Implementation: A process evaluation of pathway implementation will be conducted to 1) quantitatively evaluate fidelity, 2) qualitatively assess acceptability (Estimate 1100 clinicians).
- Masking
- None (open label)
- Enrolment
- 19,916 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Collaborators
- Alberta Health services
- Responsible party
- Principal investigator, Ken Kuljit Parhar, MD, University of Calgary
- Investigators
- Ken K Parhar, MD, MSc, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04744298
- Sponsor's protocol ID
- REB20-0646
- Status last verified
- Apr 2026
- First submitted
- 1 Feb 2021
- Last updated
- 7 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Krewulak KD, Knight G, Irwin A, Morrissey J, Stelfox HT, Bagshaw SM, Zuege D, Roze des Ordons A, Fiest K, Parhar KKS. Acceptability of the Venting Wisely pathway for use in critically ill adults with hypoxaemic respiratory failure and acute respiratory distress syndrome (ARDS): a qualitative study protocol. BMJ Open. 2024 May 28;14(5):e075086. doi: 10.1136/bmjopen-2023-075086.
PubMed 38806421Parhar KKS, Soo A, Knight G, Fiest K, Niven DJ, Rubenfeld G, Scales D, Stelfox HT, Zuege DJ, Bagshaw S. Protocol and statistical analysis plan for the identification and treatment of hypoxemic respiratory failure and acute respiratory distress syndrome with protection, paralysis, and proning: A type-1 hybrid stepped-wedge cluster randomised effectiveness-implementation study. Crit Care Resusc. 2023 Dec 13;25(4):207-215. doi: 10.1016/j.ccrj.2023.10.008. eCollection 2023 Dec.
PubMed 38234326