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An Anesthesia-Centered Bundle to Reduce Postoperative Pulmonary Complications: The PRIME-AIR Study (PRIME-AIR)

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ClinicalTrials.gov Identifier: NCT04108130
Recruitment Status : Recruiting
First Posted : September 27, 2019
Last Update Posted : August 5, 2020
Sponsor:
Information provided by (Responsible Party):
Marcos Vidal Melo, Massachusetts General Hospital

Brief Summary:
Postoperative pulmonary complications (PPCs) are a major cause of morbidity and mortality in surgical patients. National estimates suggest 1,062,000 PPCs per year, with 46,200 deaths, and 4.8 million additional days of hospitalization. Abdominal surgery is the field with the largest absolute number of PPCs. Our long-term goal is to develop and implement perioperative strategies to eliminate PPCs. Whereas PPCs are as significant and lethal as cardiac complications, research in the field has received much less attention, and strategies to minimize PPCs are regrettably limited. Recently, we and others have suggested a crucial role of anesthesia related interventions such as ventilatory strategies, and administration and reversal of neuromuscular blocking agents in reducing PPCs. These findings are consistent with the beneficial effects of lung protective ventilation during the adult respiratory distress syndrome (ARDS). While surgical patients differ substantially from ARDS patients as most have no or limited lung injury at the start of surgery, intraoperative anesthetic and abdominal surgery interventions result in lung derecruitment and predispose to or produce direct and indirect, potentially multiple-hit, lung injury. Thus, effective anesthetic strategies aiming at early lung protection in this group of patients are greatly needed. Indeed, the current lack of evidence results in wide and unexplained variability in anesthetic practices creating a major public health issue as some practices within usual care appear to be suboptimal and even potentially injurious. We hypothesize that an anesthesia-centered bundle, based on our recent findings and focused on perioperative lung protection, will minimize multiple and synergistic factors responsible for the multiple-hit perioperative pulmonary dysfunction and result in decreased incidence and severity of PPCs. Founded on strong preliminary data, we will leverage a network of US academic centers to study this hypothesis in two aims: Aim 1. To compare the number and severity of PPCs in patients receiving an individualized perioperative anesthesia-centered bundle to those in patients receiving usual anesthetic care during open abdominal surgery. For this, we propose to conduct a prospective multicenter randomized controlled pragmatic trial with a blinded assessor in a total of 750 patients. The bundle will consist of optimal mechanical ventilation comprising individualized positive end-expiratory pressure to maximize respiratory system compliance and minimize driving pressures, individualized use of neuromuscular blocking agents and their reversal, and postoperative lung expansion and early mobilization; Aim 2. To assess the effect of the proposed bundle on plasma levels of lung injury biomarkers. We theorize that our intervention will minimize overinflation and atelectasis reducing plasma levels of biomarkers of lung inflammatory, epithelial, and endothelial injury. Such mechanistic insights will facilitate bundle dissemination and support adoption as it has for lung protective ventilation for ARDS. At the end of this project, we expect to change clinical practice by establishing a new and clinically feasible anesthesia-centered strategy to reduce perioperative lung morbidity.

Condition or disease Intervention/treatment Phase
Postoperative Pulmonary Complications Other: Preoperative Education Procedure: Intraoperative PEEP Individualization Other: Individualization of Neuromuscular Blockade Procedure: Postoperative Incentive Spirometry Behavioral: Postoperative Ambulation Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 750 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: An Anesthesia-Centered Bundle to Reduce Postoperative Pulmonary Complications: The PRIME-AIR Study
Actual Study Start Date : January 27, 2020
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : April 2024

Arm Intervention/treatment
No Intervention: Usual Care
Patients in this arm will receive usual anesthetic and postoperative care as provided in each site.
Experimental: Intervention
This arm will receive the bundle of interventions.
Other: Preoperative Education
Brochure and video about relevance of postoperative pulmonary complications, postoperative mobilization and use of incentive spirometry.

Procedure: Intraoperative PEEP Individualization
PEEP will be set by maximizing respiratory system compliance along a decremental PEEP titration following an incremental recruitment maneuver.

Other: Individualization of Neuromuscular Blockade
Administration of neuromuscular blocking agents and their reversal will be done based on established protocol.

Procedure: Postoperative Incentive Spirometry
Patients will be encouraged to adhere to incentive spirometry to be started 2 hours after surgery and maintained until patient freely ambulates. Supervision will be provided 3 times/day for continuous education and management of barriers to optimal performance.

Behavioral: Postoperative Ambulation
Patients will be encouraged to adhere to prescription of early ambulation.




Primary Outcome Measures :
  1. Number and Severity of Postoperative Pulmonary Complications between Patient Groups [ Time Frame: Postoperative Days 0 through 7 ]
    The distribution of the number and severity of post-operative pulmonary complications (PPCs) between the control and intervention groups during the first 7 days after surgery.


Secondary Outcome Measures :
  1. All-Cause Postoperative Mortality [ Time Frame: Postoperative Days 0 through 7, 30, and 90 ]
    Mortality for any cause within 7, 30, and 90 days after the day of surgery.

  2. Grade 3 and 4 Postoperative Pulmonary Complications [ Time Frame: Postoperative Days 30 and 90 ]
    Individual grade 3 and 4 postoperative pulmonary complications within 30 and 90 days after the day of the surgery.

  3. Presence of Individual Components of Postoperative Pulmonary Complications in the Primary Endpoint [ Time Frame: Postoperative Days 0 through 7, 30, and 90 ]
    Presence of each of the individual components of the list of pulmonary complications in the primary endpoint within 7, 30, and 90 days after the day of the surgery.

  4. Rate of Intraoperative Adverse Events [ Time Frame: Days 0 through 7, 30, and 90 ]
    Rate of intraoperative adverse events (hypoxemia, hypotension during lung recruitment, need for vasoactive medications and volume replacement, muscle weakness. This will be assessed as Train Of Four scores less than 0.9 after extubation, or, in the absence of quantitative assessment, clinical assessments such as inability to generate a tidal volume above 4 mili-Liters per kilogram of predicted body weight, PBW, at time of extubation or to maintain sustained hand grip or 5-s head lift, presence of diplopia or ventilatory failure after extubation).

  5. Rate of Major Extrapulmonary Complications [ Time Frame: Days 0, 7, 30, and 90 ]
    Rate of extrapulmonary complications defined based on existing diagnosis in the medical chart.

  6. Length of Stay in Post-Anesthesia Care [ Time Frame: Days 0 through 7, 30, and 90 ]
    Length of stay in post-anesthesia care after the day of surgery until discharge.

  7. Length of Postoperative Oxygen Support [ Time Frame: Day 0 ]
    Number of time (hours or days) spent in the postoperative oxygen therapy or other respiratory support

  8. Unexpected Readmission to ICU [ Time Frame: After date of discharge to day 90 ]
    The incidence of an unexpected admission to the Intensive Care Unit after the day of discharge from the surgery.

  9. Length of ICU stay [ Time Frame: After date of discharge to day 90 ]
    The number of days in the Intensive Care Unit, if admitted.

  10. Length of Hospital Stay [ Time Frame: Days 0 through 7, 30, and 90 ]
    Number of days the participant has spent in the hospital since the day of the surgery.

  11. Incidence of Other Hospital Readmission(s) After Initial Discharge [ Time Frame: After the date of discharge to day 90 ]
    The incidence of hospital readmission(s), other than to the Intensive Care Unit, if admitted.

  12. Difference in Fatigue Patient-Reported Outcomes Measurements Information System (PROMIS) scores [ Time Frame: Baseline (pre-Day 0), Days 7, 30, and 90 ]

    PROMIS is system of individual scales (e.g., Fatigue PROMIS measure, Dyspnea PROMIS measure) to quantify the physical, mental, and social health outcomes of a patient surrounding a particular health issue. The short form for both the Fatigue PROMIS measure will be used for the current study.

    Items on the Fatigue PROMIS measure are rated on a 5-point Likert-type scale (1-5), where 1 most often means "not at all" and 5 most often means "very much". Some items are reverse-coded.

    Total T-scores will be used in the analysis of the current study. T-scores are derived from the total raw scale scores (sum of each item on the scale). Lower values represent a better outcome and higher values represent a worse outcome.

    Fatigue PROMIS T-scores will be compared at 4 time-points.


  13. Difference in Dyspnea Patient-Reported Outcomes Measurements Information System (PROMIS) scores [ Time Frame: Baseline (pre-Day 0), Days 7, 30, and 90 ]

    PROMIS is system of individual scales (e.g., Fatigue PROMIS measure, Dyspnea PROMIS measure) to quantify the physical, mental, and social health outcomes of a patient surrounding a particular health issue. The short form for both the Dyspnea PROMIS measure will be used for the current study.

    Items on the Dyspnea PROMIS measure are rated on a 4-point Likert-type scale (0-3), were 0 means "no difficulty" and 3 means "much difficulty". Each item also allows the patient to enter a missing value (X).

    Total T-scores will be used in the analysis of the current study. T-scores are derived from the total raw scale scores (sum of each item on the scale). Lower values represent a better outcome and higher values represent a worse outcome.

    Dyspnea PROMIS T-scores will be compared at 4 time-points.




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults (>=18 years) scheduled for elective surgery with expected duration >=2 hours
  • Open abdominal surgery including: gastric, biliary, pancreatic, hepatic, major bowel, ovarian, renal tract, bladder, prostatic, radical hysterectomy, and pelvic exenteration
  • Intermediate or high risk of PPCs defined by an ARISCAT risk score>=26

Exclusion Criteria:

  • Inability or refusal to provide consent
  • Inability or significant difficulty to perform any study interventions, including incentive spirometry, ambulation and/or maintaining follow-up contact with study personnel for up to 90 days after the date of surgery.
  • Participation in any interventional research study within 30 days of the time of the study.
  • Previous surgery within 30 days prior to this study.
  • Pregnancy
  • Emergency surgery
  • Severe obesity (above Class I, BMI>=35 kg/m2)
  • Significant lung disease: any diagnosed or treated respiratory condition that (a) requires home oxygen therapy or non-invasive ventilation (except nocturnal treatment of sleep apnea without supplemental oxygen), (b) severely limits exercise tolerance to <4 METs (e.g., patients unable to do light housework, walk flat at 4 miles/h or climb one flight of stairs), (c) required previous lung surgery, or (d) includes presence of severe pulmonary emphysema or bullae
  • Significant heart disease: cardiac conditions that limit exercise tolerance to <4 METs
  • Renal failure: peritoneal or hemodialysis requirement or preoperative creatinine >=2 mg/dL
  • Neuromuscular disease that impairs ability to ventilate without assistance
  • Severe chronic liver disease (Child-Turcotte-Pugh Score >9, Appendix I)
  • Sepsis
  • Malignancy or other irreversible condition for which 6-month mortality is estimated >=20%
  • Bone marrow transplant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04108130


Contacts
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Contact: Marcos F Vidal Melo, MD 6177264654 mvidalmelo@partners.org
Contact: Ana Fernandez-Bustamante, MD ANA.FERNANDEZ-BUSTAMANTE@UCDENVER.EDU

Locations
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United States, California
University of California - San Francisco Recruiting
San Francisco, California, United States, 94115
Contact: Jae-Woo Lee, M.D.    415-476-0452    jae-woo.lee@ucsf.edu   
United States, Colorado
University of Colorado, Anschutz Medical Campus Recruiting
Aurora, Colorado, United States, 80045
Contact: Ana Fernandez-Bustamante, M.D., Ph.D.    720-273-1335    ana.fernandez-bustamante@cuanschutz.edu   
United States, Illinois
Northwestern University Not yet recruiting
Evanston, Illinois, United States, 60208
Contact: Ravindra Alok Gupta, M.D.       ravindra.gupta@nm.org   
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Marcos Vidal Melo, MD    617-726-4654      
Contact: Ahmed Hassan, MD    6177268719      
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Gyorgy Frendl, MD    617-732-5910      
Beth Israel Deaconess Hospital Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Balachundhar Subramaniam, M.D.    617-667-3112    bsubrama@bidmc.harvard.edu   
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
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Principal Investigator: Marcos F Vidal Melo, MD Massachusetts General Hospital
Publications:
Writing Committee for the PROBESE Collaborative Group of the PROtective VEntilation Network (PROVEnet) for the Clinical Trial Network of the European Society of Anaesthesiology, Bluth T, Serpa Neto A, Schultz MJ, Pelosi P, Gama de Abreu M; PROBESE Collaborative Group, Bluth T, Bobek I, Canet JC, Cinnella G, de Baerdemaeker L, Gama de Abreu M, Gregoretti C, Hedenstierna G, Hemmes SNT, Hiesmayr M, Hollmann MW, Jaber S, Laffey J, Licker MJ, Markstaller K, Matot I, Mills GH, Mulier JP, Pelosi P, Putensen C, Rossaint R, Schmitt J, Schultz MJ, Senturk M, Serpa Neto A, Severgnini P, Sprung J, Vidal Melo MF, Wrigge H. Effect of Intraoperative High Positive End-Expiratory Pressure (PEEP) With Recruitment Maneuvers vs Low PEEP on Postoperative Pulmonary Complications in Obese Patients: A Randomized Clinical Trial. JAMA. 2019 Jun 18;321(23):2292-2305. doi: 10.1001/jama.2019.7505. Erratum in: JAMA. 2019 Nov 12;322(18):1829-1830.
Ferrando C, Soro M, Unzueta C, Suarez-Sipmann F, Canet J, Librero J, Pozo N, Peiró S, Llombart A, León I, India I, Aldecoa C, Díaz-Cambronero O, Pestaña D, Redondo FJ, Garutti I, Balust J, García JI, Ibáñez M, Granell M, Rodríguez A, Gallego L, de la Matta M, Gonzalez R, Brunelli A, García J, Rovira L, Barrios F, Torres V, Hernández S, Gracia E, Giné M, García M, García N, Miguel L, Sánchez S, Piñeiro P, Pujol R, García-Del-Valle S, Valdivia J, Hernández MJ, Padrón O, Colás A, Puig J, Azparren G, Tusman G, Villar J, Belda J; Individualized PeRioperative Open-lung VEntilation (iPROVE) Network. Individualised perioperative open-lung approach versus standard protective ventilation in abdominal surgery (iPROVE): a randomised controlled trial. Lancet Respir Med. 2018 Mar;6(3):193-203. doi: 10.1016/S2213-2600(18)30024-9. Epub 2018 Jan 19.

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Responsible Party: Marcos Vidal Melo, Director of Cardiac Anesthesia Research; Professor of Anesthesia, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT04108130    
Other Study ID Numbers: HL140177
First Posted: September 27, 2019    Key Record Dates
Last Update Posted: August 5, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: We will comply with the NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information (NOT-OD-16-149) and NIH/NHLBI guidelines. We will submit data and specimens to the NHLBI BioLINCC repository, and follow procedures specified in The BioLINCC Handbook. The first step is the assembly and submission of a list of material as we will also submit specimens to the NHLBI biorepository. The second step will be to prepare a data redaction plan removing personal identifiers and administrative data. We will recode low-frequency data values to protect subject privacy. After we complete redaction, we will prepare study data set documentation, a summary of the changes and deletions during the redaction process, and a summary document. We will submit the data to the BioLINCC repository following the standard procedures. We will comply with any modifications identified during the BioLINCC repository review, and submit final material acceptable to the repository.
Supporting Materials: Study Protocol
Time Frame: After conclusion of the study, planned for 5 years.
Access Criteria: According to the NIH/NHLBI access policies.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No