Identification and Treatment of Hypoxemic Respiratory Failure and ARDS With Protection, Paralysis, and Proning Pathway

• Sponsor: University of Calgary (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04744298
• Collaborator: Alberta Health services (Other)
• Enrollment: 3,522
• Locations: 17
• Arm: 1
• Anticipated Duration (Months): 20
• Patients Per Site: 207.2
• Patients Per Site Per Month: 10.4

Study Details

Study Description

Brief 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. 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.

Condition or Disease	Intervention/Treatment	Phase
Acute Respiratory Distress Syndrome; Hypoxemic Respiratory Failure; ARDS, Human	Other: TheraPPP	N/A

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:

1. Effectiveness of the pathway. A cost-effectiveness analysis is a secondary objective.

2. 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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 3522 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: The study will use an effectiveness-implementation hybrid study 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 Intensive Care Units (ICUs). The unit of randomization will be a cluster of two ICUs. The intervention will be implemented into one cluster every two 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 27 months (Estimate: 2496 patients). The comparison (control) therapy will be usual management assessed in the baseline period. Implementation: A process evaluation of TheraPPP pathway implementation will be conducted to 1) quantitatively evaluate fidelity, 2) qualitatively assess acceptability (Estimate 1048 clinicians).The study will use an effectiveness-implementation hybrid study 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 Intensive Care Units (ICUs). The unit of randomization will be a cluster of two ICUs. The intervention will be implemented into one cluster every two 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 27 months (Estimate: 2496 patients). The comparison (control) therapy will be usual management assessed in the baseline period. Implementation: A process evaluation of TheraPPP pathway implementation will be conducted to 1) quantitatively evaluate fidelity, 2) qualitatively assess acceptability (Estimate 1048 clinicians).
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Identification and Treatment of Hypoxemic Respiratory Failure (HRF) and ARDS With Protection, Paralysis, and Proning: TheraPPP Study
• Actual Study Start Date: Apr 1, 2021
• Anticipated Primary Completion Date: Dec 1, 2022
• Anticipated Study Completion Date: Dec 1, 2022

Arms and Interventions

Arm

Intervention/Treatment

Experimental: TheraPPP Pathway 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 27 months. To assess acceptability of the pathway the investigators will conduct a survey and focus groups to clinicians who used the Pathway.

Other: TheraPPP; 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.

Outcome Measures

Primary Outcome Measures

1. EFFECTIVENESS (primary clinical outcome) 28-day ventilator free days [4 months (after the study post-intervention period)]

   A composite outcome of survival and days spent not ventilated over the first 28 days

2. EFFECTIVENESS (primary economic outcome) Cost per ventilator free day saved [4 months (after the study post-intervention period)]

   Cost per ventilator free day saved from the perspective of the health care system over the index hospitalization period

3. IMPLEMENTATION (primary fidelity outcome) Composite Fidelity Score [4 months (after the study post-intervention period)]

   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 ≥24 hours, 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 stratified by volume and pressure control (step2/3) 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)

4. IMPLEMENTATION (primary acceptability outcome) Theoretical Framework of Acceptability - Composite Acceptability Score [4 months (after the study post-intervention period)]

   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 5 or above from a 7-point Likert scale, in which 1 indicates strong disagreement (and lower acceptability) and 7 indicates strong agreement (and higher acceptability).

Secondary Outcome Measures

1. Days of safe ventilation [4 months (after the study post-intervention period)]

   Proportion of patient-days on controlled ventilation with median daily tidal volume less than or equal to 8mL/kg predicted body weight in patients who are eligible

2. Proportion of days of safe ventilation in females [4 months (after the study post-intervention period)]

   Days of safe ventilation for females (proportion of days of safe ventilation with a median daily tidal volume ≤ 8 mL/kg predicted body weight)

3. 28-day and hospital survival [90 days]

   Number of patients who die in the ICU, hospital, and at or before 28-day hospital censored at 90 days

4. Total cost: ICU admission [4 months (after the study post-intervention period)]

   Total cost for the ICU admission

5. Total cost: Index hospitalization [4 months (after the study post-intervention period)]

   Total cost for the index hospitalization

6. ICU and hospital length of stay [4 months (after the study post-intervention period)]

   The number of days that patients stay in the ICU and in hospital

7. Cost per quality adjusted life year (QALY) [4 months (after the study post-intervention period)]

   Cost per quality adjusted life year (QALY) from the health care system perspective over the patient's lifetime

8. The proportion of patients ventilated ≥24 hours with a height measured [4 months (after the study post-intervention period)]

   Total number of ventilated patients for ≥24 hours with a height measured divided by the total number of patients ventilated ≥24 hours

9. Proportion of patient days with PF ratio ≤300 with a tidal volume ≤8mL/kg stratified by volume and pressure control [4 months (after the study post-intervention period)]

   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 stratified by volume and pressure control

10. Proportion of patient days with PF ratio ≤300 with a plateau pressure measured [4 months (after the study post-intervention period)]

    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

11. Proportion of patient days with HRF and PF ratio ≤150 who receive neuromuscular blockade [4 months (after the study post-intervention period)]

    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

12. Proportion of patient days with HRF and PF ratio ≤100 who receive neuromuscular blockade [4 months (after the study post-intervention period)]

    The number of patient days with HRF and PF ratio ≤100 who receive neuromuscular blockade divided by the number of patient days with HRF and PF ratio ≤100

13. Proportion of patient days with HRF and PF ratio ≤150 and FiO2 ≥0.6 receiving prone ventilation [4 months (after the study post-intervention period)]

    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

14. The proportion of patient days with HRF and PF ratio ≤100 and FiO2 ≥0.6 receiving prone ventilation [4 months (after the study post-intervention period)]

    The number of patient days with HRF and PF ratio ≤100 and FiO2 ≥0.6 receiving prone ventilation divided by the number of patient days with HRF and PF ratio ≤100 and FiO2 ≥0.6

15. Proportion of patients receiving rescue therapies [4 months (after the study post-intervention period)]

    The proportion of patients receiving rescue therapies including inhaled vasodilators, Extracorporeal Life Support

16. Theoretical Framework of Acceptability - Opportunity costs construct [4 months (after the study post-intervention period)]

    Benefits or costs to the participant for using the pathway graded on a 7-point Likert scale in which 1 indicates strong disagreement (and lower acceptability) and 7 indicates strong agreement (and higher acceptability), Median (IQR)

17. Theoretical Framework of Acceptability - Perceived effectiveness construct [4 months (after the study post-intervention period)]

    The extent to which the intervention is perceived as likely to achieve its purpose graded graded on a 7-point Likert scale in which 1 indicates strong disagreement (and lower acceptability) and 7 indicates strong agreement (and higher acceptability), Median (IQR)

18. Theoretical Framework of Acceptability - Affective attitude construct [4 months (after the study post-intervention period)]

    How an individual feels about the intervention graded on a 7-point Likert scale in which 1 indicates strong disagreement (and lower acceptability) and 7 indicates strong agreement (and higher acceptability), Median (IQR)

19. Theoretical Framework of Acceptability - Burden construct [4 months (after the study post-intervention period)]

    The perceived amount of effort that is required to participate in the intervention graded on a 7-point Likert scale in which 1 indicates strong disagreement (and lower acceptability) and 7 indicates strong agreement (and higher acceptability), Median (IQR)

20. Theoretical Framework of Acceptability - Ethicality construct [4 months (after the study post-intervention period)]

    The extent to which the intervention has a good fit with an individual's value graded on a 7-point Likert scale in which 1 indicates strong disagreement (and lower acceptability) and 7 indicates strong agreement (and higher acceptability), Median (IQR)

21. Theoretical Framework of Acceptability - Self efficacy construct [4 months (after the study post-intervention period)]

    The participant's confidence that they can perform the behavior(s) required to participate in the intervention graded on a 7-point Likert scale in which 1 indicates strong disagreement (and lower acceptability) and 7 indicates strong agreement (and higher acceptability), Median (IQR)

22. Theoretical Framework of Acceptability - Intervention coherence construct [4 months (after the study post-intervention period)]

    The extent to which the participant understands the invention and how it works graded on a 7-point Likert scale in which 1 indicates strong disagreement (and lower acceptability) and 7 indicates strong agreement (and higher acceptability), Median (IQR)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Admitted to the one of the 17 adult Intensive Care Units in Alberta

• Invasively mechanically ventilated

Exclusion Criteria:

• none

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Peter Lougheed Centre (PLC)	Calgary	Alberta	Canada	T1Y 6J4
2	Foothills Hospital Intensive Care Unit	Calgary	Alberta	Canada	T2N 2T9
3	Foothills Medical Center Cardiovascular ICU	Calgary	Alberta	Canada	T2N 2T9
4	Rockyview General Hospital	Calgary	Alberta	Canada	T2V 1P9
5	South Health Campus	Calgary	Alberta	Canada	T3M 1M4
6	Royal Alexandra Hospital	Edmonton	Alberta	Canada	T5H 3V9
7	Misericordia Community Hospital	Edmonton	Alberta	Canada	T5R 4H5
8	Mazankowski Alberta Heart Institute	Edmonton	Alberta	Canada	T6G 2B7
9	University of Alberta Hospital General Systems ICU	Edmonton	Alberta	Canada	T6G 2B7
10	University of Alberta Hospital Neurosciences Intensive Care Unit	Edmonton	Alberta	Canada	T6G 2B7
11	Grey Nuns Community Hospital	Edmonton	Alberta	Canada	T6L 5X8
12	Northern Lights Regional Health Centre	Fort McMurray	Alberta	Canada	T9H 1P2
13	Queen Elizabeth II Hospital	Grande Prairie	Alberta	Canada	T8V 2E8
14	Chinook Regional Hospital	Lethbridge	Alberta	Canada	T1J 1W5
15	Medicine Hat Regional Hospital	Medicine Hat	Alberta	Canada	T1A 4H6
16	Red Deer Regional Hospital Centre	Red Deer	Alberta	Canada	T4N 4E7
17	Sturgeon Community Hospital	St. Albert	Alberta	Canada	T8N 6C4

Sponsors and Collaborators

• University of Calgary
• Alberta Health services

Investigators

• Principal Investigator: Ken K Parhar, MD, MSc, University of Calgary

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ken Kuljit Parhar, MD, Consultant Intensivist & Clinical Assistant Professor Affiliation: University of Calgary, University of Calgary
• ClinicalTrials.gov Identifier: NCT04744298
• Other Study ID Numbers: REB20-0646
• First Posted: Feb 8, 2021
• Last Update Posted: Jul 22, 2022
• Last Verified: Jul 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Respiratory Insufficiency; Acute Lung Injury; Paralysis

Study Results

No Results Posted as of Jul 22, 2022