Effect of the Pulmonary Embolism Rule-Out Criteria on Subsequent Thromboembolic Events Among Low-Risk Emergency Department Patients: The PROPER Randomized Clinical Trial

doi:10.1001/jama.2017.21904

Randomized Controlled Trial

. 2018 Feb 13;319(6):559-566.

doi: 10.1001/jama.2017.21904.

Effect of the Pulmonary Embolism Rule-Out Criteria on Subsequent Thromboembolic Events Among Low-Risk Emergency Department Patients: The PROPER Randomized Clinical Trial

Yonathan Freund^{1

2}, Marine Cachanado³, Adeline Aubry², Charlotte Orsini⁴, Pierre-Alexis Raynal⁵, Anne-Laure Féral-Pierssens⁶, Sandrine Charpentier⁷, Florence Dumas⁸, Nacera Baarir⁹, Jennifer Truchot¹⁰, Thibaut Desmettre¹¹, Karim Tazarourte¹², Sebastien Beaune¹³, Agathe Leleu¹⁴, Mehdi Khellaf¹⁵, Mathias Wargon¹⁶, Ben Bloom¹⁷, Alexandra Rousseau³, Tabassome Simon^{1

3}, Bruno Riou^{1

2}; PROPER Investigator Group

Affiliations

¹ Sorbonne Université, INSERM UMRS 1166, IHU ICAN, Paris, France.
² Emergency Department, Hôpital Universitaire Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
³ Clinical Research Platform (URC-CRC-CRB), AP-HP Hôpital Saint-Antoine, Paris, France.
⁴ Emergency Department, Hôpital Avicenne, APHP, Bobigny, France.
⁵ Emergency Department, Hôpital Saint-Antoine, APHP, Paris, France.
⁶ Emergency Department, Hôpital Européen Georges Pompidou, APHP, Paris, France.
⁷ Université Toulouse III Paul Sabatier, INSERM UMR 1027, CHU Toulouse, Toulouse, Emergency Department, Toulouse, France.
⁸ Université Paris Descartes, INSERM UMR970, APHP, Emergency Department, Hôpital Cochin, Paris, France.
⁹ Emergency Department, Hôpital Tenon, APHP, Paris, France.
¹⁰ Emergency Department, Hôpital Lariboisière, APHP, Paris, France.
¹¹ Université Bourgogne Franche-Comté, Emergency Department, CHRU Minjoz, Besançon, France.
¹² Université Claude Bernard Lyon1, HESPER EA 7425, Hospices Civils de Lyon, Emergency Department, Hôpital Edouard Herriot, Lyon, France.
¹³ Emergency Department, Hôpital Ambroise-Paré, APHP, Boulogne, France.
¹⁴ Emergency Department, Hôpital Bichat, APHP, Paris, France.
¹⁵ Université Paris Est, INSERM U955, APHP, Emergency Department, Hôpital Henri Mondor, Créteil, France.
¹⁶ Emergency Department, Hôpital Saint Camille, Bry sur Marne, France.
¹⁷ Emergency Department, Barts Health NHS Trust, London, United Kingdom.

PMID: 29450523
PMCID: PMC5838786
DOI: 10.1001/jama.2017.21904

Randomized Controlled Trial

Effect of the Pulmonary Embolism Rule-Out Criteria on Subsequent Thromboembolic Events Among Low-Risk Emergency Department Patients: The PROPER Randomized Clinical Trial

Yonathan Freund et al. JAMA. 2018.

. 2018 Feb 13;319(6):559-566.

doi: 10.1001/jama.2017.21904.

Authors

Affiliations

¹ Sorbonne Université, INSERM UMRS 1166, IHU ICAN, Paris, France.
² Emergency Department, Hôpital Universitaire Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
³ Clinical Research Platform (URC-CRC-CRB), AP-HP Hôpital Saint-Antoine, Paris, France.
⁴ Emergency Department, Hôpital Avicenne, APHP, Bobigny, France.
⁵ Emergency Department, Hôpital Saint-Antoine, APHP, Paris, France.
⁶ Emergency Department, Hôpital Européen Georges Pompidou, APHP, Paris, France.
⁷ Université Toulouse III Paul Sabatier, INSERM UMR 1027, CHU Toulouse, Toulouse, Emergency Department, Toulouse, France.
⁸ Université Paris Descartes, INSERM UMR970, APHP, Emergency Department, Hôpital Cochin, Paris, France.
⁹ Emergency Department, Hôpital Tenon, APHP, Paris, France.
¹⁰ Emergency Department, Hôpital Lariboisière, APHP, Paris, France.
¹¹ Université Bourgogne Franche-Comté, Emergency Department, CHRU Minjoz, Besançon, France.
¹² Université Claude Bernard Lyon1, HESPER EA 7425, Hospices Civils de Lyon, Emergency Department, Hôpital Edouard Herriot, Lyon, France.
¹³ Emergency Department, Hôpital Ambroise-Paré, APHP, Boulogne, France.
¹⁴ Emergency Department, Hôpital Bichat, APHP, Paris, France.
¹⁵ Université Paris Est, INSERM U955, APHP, Emergency Department, Hôpital Henri Mondor, Créteil, France.
¹⁶ Emergency Department, Hôpital Saint Camille, Bry sur Marne, France.
¹⁷ Emergency Department, Barts Health NHS Trust, London, United Kingdom.

PMID: 29450523
PMCID: PMC5838786
DOI: 10.1001/jama.2017.21904

Abstract

Importance: The safety of the pulmonary embolism rule-out criteria (PERC), an 8-item block of clinical criteria aimed at ruling out pulmonary embolism (PE), has not been assessed in a randomized clinical trial.

Objective: To prospectively validate the safety of a PERC-based strategy to rule out PE.

Design, setting, and patients: A crossover cluster-randomized clinical noninferiority trial in 14 emergency departments in France. Patients with a low gestalt clinical probability of PE were included from August 2015 to September 2016, and followed up until December 2016.

Interventions: Each center was randomized for the sequence of intervention periods. In the PERC period, the diagnosis of PE was excluded with no further testing if all 8 items of the PERC rule were negative.

Main outcomes and measures: The primary end point was the occurrence of a thromboembolic event during the 3-month follow-up period that was not initially diagnosed. The noninferiority margin was set at 1.5%. Secondary end points included the rate of computed tomographic pulmonary angiography (CTPA), median length of stay in the emergency department, and rate of hospital admission.

Results: Among 1916 patients who were cluster-randomized (mean age 44 years, 980 [51%] women), 962 were assigned to the PERC group and 954 were assigned to the control group. A total of 1749 patients completed the trial. A PE was diagnosed at initial presentation in 26 patients in the control group (2.7%) vs 14 (1.5%) in the PERC group (difference, 1.3% [95% CI, -0.1% to 2.7%]; P = .052). One PE (0.1%) was diagnosed during follow-up in the PERC group vs none in the control group (difference, 0.1% [95% CI, -∞ to 0.8%]). The proportion of patients undergoing CTPA in the PERC group vs control group was 13% vs 23% (difference, -10% [95% CI, -13% to -6%]; P < .001). In the PERC group, rates were significantly reduced for the median length of emergency department stay (mean reduction, 36 minutes [95% CI, 4 to 68]) and hospital admission (difference, 3.3% [95% CI, 0.1% to 6.6%]).

Conclusions and relevance: Among very low-risk patients with suspected PE, randomization to a PERC strategy vs conventional strategy did not result in an inferior rate of thromboembolic events over 3 months. These findings support the safety of PERC for very low-risk patients presenting to the emergency department.

Trial registration: clinicaltrials.gov Identifier: NCT02375919.

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Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Freund reports receipt of nonfinancial support from Sanofi, and lecture fees from Bristol-Myers Squibb and AstraZeneca outside the submitted work. Dr Simon reports receipt of a grant from the Delegation for Clinical Research and Innovation (DRCI [APHP]) during the conduct of the study; grants from AstraZeneca, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, sanofi-aventis, and Pfizer; and personal fees for board membership, consultancy services, or lecture fees from AstraZeneca, Bristol-Myers Squibb, Novartis, and sanofi-aventis outside the submitted work. No other disclosures were reported.

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Comment in

Utility of a Clinical Prediction Rule to Exclude Pulmonary Embolism Among Low-Risk Emergency Department Patients: Reason to PERC Up.
Kline JA. Kline JA. JAMA. 2018 Feb 13;319(6):551-553. doi: 10.1001/jama.2017.21901. JAMA. 2018. PMID: 29450510 No abstract available.
PERC strategy was noninferior to the usual strategy for ruling out PE in low-risk patients in the ED.
Raja AS. Raja AS. Ann Intern Med. 2018 May 15;168(10):JC54. doi: 10.7326/ACPJC-2018-168-10-054. Ann Intern Med. 2018. PMID: 29800430 No abstract available.

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References

1. Konstantinides SV, Torbicki A, Agnelli G, et al. . 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2014;35(43):3033-3069, 3069a-3069k.. - PubMed
1. van Belle A, Büller HR, Huisman MV, et al. ; Christopher Study Investigators . Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. JAMA. 2006;295(2):172-179. - PubMed
1. Wiener RS, Schwartz LM, Woloshin S. Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Arch Intern Med. 2011;171(9):831-837. - PMC - PubMed
1. Wiener RS, Schwartz LM, Woloshin S. When a test is too good: how CT pulmonary angiograms find pulmonary emboli that do not need to be found. BMJ. 2013;347(jul02):f3368-f3368.. - PMC - PubMed
1. Kline JA, Mitchell AM, Kabrhel C, Richman PB, Courtney DM. Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism. J Thromb Haemost. 2004;2(8):1247-1255. - PubMed

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[1] Konstantinides SV, Torbicki A, Agnelli G, et al. . 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2014;35(43):3033-3069, 3069a-3069k.. - PubMed

[2] Konstantinides SV, Torbicki A, Agnelli G, et al. . 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2014;35(43):3033-3069, 3069a-3069k.. - PubMed

[3] van Belle A, Büller HR, Huisman MV, et al. ; Christopher Study Investigators . Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. JAMA. 2006;295(2):172-179. - PubMed

[4] van Belle A, Büller HR, Huisman MV, et al. ; Christopher Study Investigators . Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. JAMA. 2006;295(2):172-179. - PubMed

[5] Wiener RS, Schwartz LM, Woloshin S. Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Arch Intern Med. 2011;171(9):831-837. - PMC - PubMed

[6] Wiener RS, Schwartz LM, Woloshin S. Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Arch Intern Med. 2011;171(9):831-837. - PMC - PubMed

[7] Wiener RS, Schwartz LM, Woloshin S. When a test is too good: how CT pulmonary angiograms find pulmonary emboli that do not need to be found. BMJ. 2013;347(jul02):f3368-f3368.. - PMC - PubMed

[8] Wiener RS, Schwartz LM, Woloshin S. When a test is too good: how CT pulmonary angiograms find pulmonary emboli that do not need to be found. BMJ. 2013;347(jul02):f3368-f3368.. - PMC - PubMed

[9] Kline JA, Mitchell AM, Kabrhel C, Richman PB, Courtney DM. Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism. J Thromb Haemost. 2004;2(8):1247-1255. - PubMed

[10] Kline JA, Mitchell AM, Kabrhel C, Richman PB, Courtney DM. Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism. J Thromb Haemost. 2004;2(8):1247-1255. - PubMed

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Effect of the Pulmonary Embolism Rule-Out Criteria on Subsequent Thromboembolic Events Among Low-Risk Emergency Department Patients: The PROPER Randomized Clinical Trial

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Effect of the Pulmonary Embolism Rule-Out Criteria on Subsequent Thromboembolic Events Among Low-Risk Emergency Department Patients: The PROPER Randomized Clinical Trial

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