Intermediate-Dose versus Standard-Dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to the Intensive Care Unit: 90-Day Results from the INSPIRATION Randomized Trial

Behnood Bikdeli; Azita H. Talasaz; Farid Rashidi; Hooman Bakhshandeh; Farnaz Rafiee; Parisa Rezaeifar; Elahe Baghizadeh; Samira Matin; Sepehr Jamalkhani; Ouria Tahamtan; Babak Sharif-Kashani; Mohammad Taghi Beigmohammadi; Mohsen Farrokhpour; Seyed Hashem Sezavar; Pooya Payandemehr; Ali Dabbagh; Keivan Gohari Moghadam; Hossein Khalili; Mahdi Yadollahzadeh; Taghi Riahi; Atefeh Abedini; Somayeh Lookzadeh; Hamid Rahmani; Elnaz Zoghi; Keyhan Mohammadi; Pardis Sadeghipour; Homa Abri; Sanaz Tabrizi; Seyed Masoud Mousavian; Shaghayegh Shahmirzaei; Ahmad Amin; Bahram Mohebbi; Seyed Ehsan Parhizgar; Rasoul Aliannejad; Vahid Eslami; Alireza Kashefizadeh; Paul P. Dobesh; Hessam Kakavand; Seyed Hossein Hosseini; Shadi Shafaghi; Samrand Fattah Ghazi; Atabak Najafi; David Jimenez; Aakriti Gupta; Mahesh V. Madhavan; Sanjum S. Sethi; Sahil A. Parikh; Manuel Monreal; Naser Hadavand; Alireza Hajighasemi; Majid Maleki; Saeed Sadeghian; Gregory Piazza; Ajay J. Kirtane; Benjamin W. Van Tassell; Gregg W. Stone; Gregory Y.H. Lip; Harlan M. Krumholz; Samuel Z. Goldhaber; Parham Sadeghipour

doi:10.1055/a-1485-2372

Intermediate-Dose versus Standard-Dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to the Intensive Care Unit: 90-Day Results from the INSPIRATION Randomized Trial

Behnood Bikdeli, Azita H. Talasaz, Farid Rashidi, Hooman Bakhshandeh, Farnaz Rafiee, Parisa Rezaeifar, Elahe Baghizadeh, Samira Matin, Sepehr Jamalkhani, Ouria Tahamtan, Babak Sharif-Kashani, Mohammad Taghi Beigmohammadi, Mohsen Farrokhpour, Seyed Hashem Sezavar, Pooya Payandemehr, Ali Dabbagh, Keivan Gohari Moghadam, Hossein Khalili, Mahdi Yadollahzadeh, Taghi RiahiAtefeh Abedini, Somayeh Lookzadeh, Hamid Rahmani, Elnaz Zoghi, Keyhan Mohammadi, Pardis Sadeghipour, Homa Abri, Sanaz Tabrizi, Seyed Masoud Mousavian, Shaghayegh Shahmirzaei, Ahmad Amin, Bahram Mohebbi, Seyed Ehsan Parhizgar, Rasoul Aliannejad, Vahid Eslami, Alireza Kashefizadeh, Paul P. Dobesh, Hessam Kakavand, Seyed Hossein Hosseini, Shadi Shafaghi, Samrand Fattah Ghazi, Atabak Najafi, David Jimenez, Aakriti Gupta, Mahesh V. Madhavan, Sanjum S. Sethi, Sahil A. Parikh, Manuel Monreal, Naser Hadavand, Alireza Hajighasemi, Majid Maleki, Saeed Sadeghian, Gregory Piazza, Ajay J. Kirtane, Benjamin W. Van Tassell, Gregg W. Stone, Gregory Y.H. Lip, Harlan M. Krumholz, Samuel Z. Goldhaber, Parham Sadeghipour

Research output: Contribution to journal › Article › peer-review

55 Scopus citations

Abstract

Background Thrombotic complications are considered among the main extrapulmonary manifestations of coronavirus disease 2019 (COVID-19). The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown. Methods This article reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study. Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status. The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death. The main safety outcome was major bleeding. Results Of 600 randomized patients, 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]: 62 [50, 71] years; 237 [42.2%] women), of whom 336 (59.8%) survived to hospital discharge. The primary outcome occurred in 132 (47.8%) of patients assigned to intermediate dose and 130 (45.4%) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.95-1.55, p = 0.11). Findings were similar for other efficacy outcomes, and in the landmark analysis from days 31 to 90 (HR: 1.59, 95% CI: 0.45-5.06). There were 7 (2.5%) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4%) major bleeding events in the standard-dose group (none fatal) (HR: 1.82, 95% CI: 0.53-6.24). Conclusion Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up.

Original language	English (US)
Pages (from-to)	131-141
Number of pages	11
Journal	Thrombosis and Haemostasis
Volume	122
Issue number	1
DOIs	https://doi.org/10.1055/a-1485-2372
State	Published - Jun 6 2021

Keywords

COVID-19
anticoagulation
enoxaparin
heparin
trial

ASJC Scopus subject areas

Hematology

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10.1055/a-1485-2372

Cite this

Bikdeli, B., Talasaz, A. H., Rashidi, F., Bakhshandeh, H., Rafiee, F., Rezaeifar, P., Baghizadeh, E., Matin, S., Jamalkhani, S., Tahamtan, O., Sharif-Kashani, B., Beigmohammadi, M. T., Farrokhpour, M., Sezavar, S. H., Payandemehr, P., Dabbagh, A., Moghadam, K. G., Khalili, H., Yadollahzadeh, M., ... Sadeghipour, P. (2021). Intermediate-Dose versus Standard-Dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to the Intensive Care Unit: 90-Day Results from the INSPIRATION Randomized Trial. Thrombosis and Haemostasis, 122(1), 131-141. https://doi.org/10.1055/a-1485-2372

Intermediate-Dose versus Standard-Dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to the Intensive Care Unit: 90-Day Results from the INSPIRATION Randomized Trial. / Bikdeli, Behnood; Talasaz, Azita H.; Rashidi, Farid et al.
In: Thrombosis and Haemostasis, Vol. 122, No. 1, 06.06.2021, p. 131-141.

Research output: Contribution to journal › Article › peer-review

Bikdeli, B, Talasaz, AH, Rashidi, F, Bakhshandeh, H, Rafiee, F, Rezaeifar, P, Baghizadeh, E, Matin, S, Jamalkhani, S, Tahamtan, O, Sharif-Kashani, B, Beigmohammadi, MT, Farrokhpour, M, Sezavar, SH, Payandemehr, P, Dabbagh, A, Moghadam, KG, Khalili, H, Yadollahzadeh, M, Riahi, T, Abedini, A, Lookzadeh, S, Rahmani, H, Zoghi, E, Mohammadi, K, Sadeghipour, P, Abri, H, Tabrizi, S, Mousavian, SM, Shahmirzaei, S, Amin, A, Mohebbi, B, Parhizgar, SE, Aliannejad, R, Eslami, V, Kashefizadeh, A, Dobesh, PP, Kakavand, H, Hosseini, SH, Shafaghi, S, Ghazi, SF, Najafi, A, Jimenez, D, Gupta, A, Madhavan, MV, Sethi, SS, Parikh, SA, Monreal, M, Hadavand, N, Hajighasemi, A, Maleki, M, Sadeghian, S, Piazza, G, Kirtane, AJ, Van Tassell, BW, Stone, GW, Lip, GYH, Krumholz, HM, Goldhaber, SZ & Sadeghipour, P 2021, 'Intermediate-Dose versus Standard-Dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to the Intensive Care Unit: 90-Day Results from the INSPIRATION Randomized Trial', Thrombosis and Haemostasis, vol. 122, no. 1, pp. 131-141. https://doi.org/10.1055/a-1485-2372

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title = "Intermediate-Dose versus Standard-Dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to the Intensive Care Unit: 90-Day Results from the INSPIRATION Randomized Trial",

abstract = "Background Thrombotic complications are considered among the main extrapulmonary manifestations of coronavirus disease 2019 (COVID-19). The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown. Methods This article reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study. Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status. The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death. The main safety outcome was major bleeding. Results Of 600 randomized patients, 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]: 62 [50, 71] years; 237 [42.2%] women), of whom 336 (59.8%) survived to hospital discharge. The primary outcome occurred in 132 (47.8%) of patients assigned to intermediate dose and 130 (45.4%) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.95-1.55, p = 0.11). Findings were similar for other efficacy outcomes, and in the landmark analysis from days 31 to 90 (HR: 1.59, 95% CI: 0.45-5.06). There were 7 (2.5%) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4%) major bleeding events in the standard-dose group (none fatal) (HR: 1.82, 95% CI: 0.53-6.24). Conclusion Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up.",

keywords = "COVID-19, anticoagulation, enoxaparin, heparin, trial",

author = "Behnood Bikdeli and Talasaz, {Azita H.} and Farid Rashidi and Hooman Bakhshandeh and Farnaz Rafiee and Parisa Rezaeifar and Elahe Baghizadeh and Samira Matin and Sepehr Jamalkhani and Ouria Tahamtan and Babak Sharif-Kashani and Beigmohammadi, {Mohammad Taghi} and Mohsen Farrokhpour and Sezavar, {Seyed Hashem} and Pooya Payandemehr and Ali Dabbagh and Moghadam, {Keivan Gohari} and Hossein Khalili and Mahdi Yadollahzadeh and Taghi Riahi and Atefeh Abedini and Somayeh Lookzadeh and Hamid Rahmani and Elnaz Zoghi and Keyhan Mohammadi and Pardis Sadeghipour and Homa Abri and Sanaz Tabrizi and Mousavian, {Seyed Masoud} and Shaghayegh Shahmirzaei and Ahmad Amin and Bahram Mohebbi and Parhizgar, {Seyed Ehsan} and Rasoul Aliannejad and Vahid Eslami and Alireza Kashefizadeh and Dobesh, {Paul P.} and Hessam Kakavand and Hosseini, {Seyed Hossein} and Shadi Shafaghi and Ghazi, {Samrand Fattah} and Atabak Najafi and David Jimenez and Aakriti Gupta and Madhavan, {Mahesh V.} and Sethi, {Sanjum S.} and Parikh, {Sahil A.} and Manuel Monreal and Naser Hadavand and Alireza Hajighasemi and Majid Maleki and Saeed Sadeghian and Gregory Piazza and Kirtane, {Ajay J.} and {Van Tassell}, {Benjamin W.} and Stone, {Gregg W.} and Lip, {Gregory Y.H.} and Krumholz, {Harlan M.} and Goldhaber, {Samuel Z.} and Parham Sadeghipour",

year = "2021",

month = jun,

day = "6",

doi = "10.1055/a-1485-2372",

language = "English (US)",

volume = "122",

pages = "131--141",

journal = "Thrombosis and Haemostasis",

issn = "0340-6245",

publisher = "Georg Thieme Verlag",

number = "1",

}

TY - JOUR

T1 - Intermediate-Dose versus Standard-Dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to the Intensive Care Unit

T2 - 90-Day Results from the INSPIRATION Randomized Trial

AU - Bikdeli, Behnood

AU - Talasaz, Azita H.

AU - Rashidi, Farid

AU - Bakhshandeh, Hooman

AU - Rafiee, Farnaz

AU - Rezaeifar, Parisa

AU - Baghizadeh, Elahe

AU - Matin, Samira

AU - Jamalkhani, Sepehr

AU - Tahamtan, Ouria

AU - Sharif-Kashani, Babak

AU - Beigmohammadi, Mohammad Taghi

AU - Farrokhpour, Mohsen

AU - Sezavar, Seyed Hashem

AU - Payandemehr, Pooya

AU - Dabbagh, Ali

AU - Moghadam, Keivan Gohari

AU - Khalili, Hossein

AU - Yadollahzadeh, Mahdi

AU - Riahi, Taghi

AU - Abedini, Atefeh

AU - Lookzadeh, Somayeh

AU - Rahmani, Hamid

AU - Zoghi, Elnaz

AU - Mohammadi, Keyhan

AU - Sadeghipour, Pardis

AU - Abri, Homa

AU - Tabrizi, Sanaz

AU - Mousavian, Seyed Masoud

AU - Shahmirzaei, Shaghayegh

AU - Amin, Ahmad

AU - Mohebbi, Bahram

AU - Parhizgar, Seyed Ehsan

AU - Aliannejad, Rasoul

AU - Eslami, Vahid

AU - Kashefizadeh, Alireza

AU - Dobesh, Paul P.

AU - Kakavand, Hessam

AU - Hosseini, Seyed Hossein

AU - Shafaghi, Shadi

AU - Ghazi, Samrand Fattah

AU - Najafi, Atabak

AU - Jimenez, David

AU - Gupta, Aakriti

AU - Madhavan, Mahesh V.

AU - Sethi, Sanjum S.

AU - Parikh, Sahil A.

AU - Monreal, Manuel

AU - Hadavand, Naser

AU - Hajighasemi, Alireza

AU - Maleki, Majid

AU - Sadeghian, Saeed

AU - Piazza, Gregory

AU - Kirtane, Ajay J.

AU - Van Tassell, Benjamin W.

AU - Stone, Gregg W.

AU - Lip, Gregory Y.H.

AU - Krumholz, Harlan M.

AU - Goldhaber, Samuel Z.

AU - Sadeghipour, Parham

PY - 2021/6/6

Y1 - 2021/6/6

N2 - Background Thrombotic complications are considered among the main extrapulmonary manifestations of coronavirus disease 2019 (COVID-19). The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown. Methods This article reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study. Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status. The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death. The main safety outcome was major bleeding. Results Of 600 randomized patients, 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]: 62 [50, 71] years; 237 [42.2%] women), of whom 336 (59.8%) survived to hospital discharge. The primary outcome occurred in 132 (47.8%) of patients assigned to intermediate dose and 130 (45.4%) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.95-1.55, p = 0.11). Findings were similar for other efficacy outcomes, and in the landmark analysis from days 31 to 90 (HR: 1.59, 95% CI: 0.45-5.06). There were 7 (2.5%) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4%) major bleeding events in the standard-dose group (none fatal) (HR: 1.82, 95% CI: 0.53-6.24). Conclusion Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up.

AB - Background Thrombotic complications are considered among the main extrapulmonary manifestations of coronavirus disease 2019 (COVID-19). The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown. Methods This article reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study. Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status. The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death. The main safety outcome was major bleeding. Results Of 600 randomized patients, 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]: 62 [50, 71] years; 237 [42.2%] women), of whom 336 (59.8%) survived to hospital discharge. The primary outcome occurred in 132 (47.8%) of patients assigned to intermediate dose and 130 (45.4%) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.95-1.55, p = 0.11). Findings were similar for other efficacy outcomes, and in the landmark analysis from days 31 to 90 (HR: 1.59, 95% CI: 0.45-5.06). There were 7 (2.5%) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4%) major bleeding events in the standard-dose group (none fatal) (HR: 1.82, 95% CI: 0.53-6.24). Conclusion Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up.

KW - COVID-19

KW - anticoagulation

KW - enoxaparin

KW - heparin

KW - trial

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U2 - 10.1055/a-1485-2372

DO - 10.1055/a-1485-2372

M3 - Article

C2 - 33865239

AN - SCOPUS:85107529660

SN - 0340-6245

VL - 122

SP - 131

EP - 141

JO - Thrombosis and Haemostasis

JF - Thrombosis and Haemostasis

IS - 1

ER -

Intermediate-Dose versus Standard-Dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to the Intensive Care Unit: 90-Day Results from the INSPIRATION Randomized Trial

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