A randomized, double-blinded, placebo-controlled pilot trial of anticoagulation in low-risk traumatic brain injury

The Delayed Versus Early Enoxaparin Prophylaxis i (DEEP I) study

Herbert Phelan, Steven E Wolf, Scott H. Norwood, Kim Aldy, Scott C. Brakenridge, Alexander Eastman, Christopher J Madden, Paul A Nakonezny, Lisa Yang, David P Chason, Gary M Arbique, John Berne, Joseph P Minei

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Abstract

BACKGROUND: Our group has created an algorithm for venous thromboembolism prophylaxis after traumatic brain injury (TBI), which stratifies patients into low, moderate, and high risk for spontaneous injury progression and tailors a prophylaxis regimen to each arm. We present the results of the Delayed Versus Early Enoxaparin Prophylaxis I study, a double-blind, placebo-controlled, randomized pilot trial on the low-risk arm. METHODS: In this two-institution study, patients presenting within 6 hours of injury with prespecified small TBI patterns and stable scans at 24 hours after injury were randomized to receive enoxaparin 30 mg bid or placebo from 24 to 96 hours after injury in a double-blind fashion. An additional computed tomography scan was obtained on all subjects 24 hours after starting treatment (and therefore 48 hours after injury). The primary end point was the radiographic worsening of TBI; secondary end points were venous thromboembolism occurrence and extracranial hemorrhagic complications. RESULTS: A total of 683 consecutive patients with TBI were screened during the 28 center months. The most common exclusions were for injuries larger than the prespecified criteria (n = 199) and preinjury anticoagulant use (n = 138). Sixty-two patients were randomized to enoxaparin (n = 34) or placebo (n = 28). Subclinical, radiographic TBI progression rates on the scans performed 48 hours after injury and 24 hours after start of treatment were 5.9% (95% confidence interval [CI], 0.7-19.7%) for enoxaparin and 3.6% (95% CI, 0.1-18.3%) for placebo, a treatment effect difference of 2.3% (95% CI, -14.42-16.5%). No clinical TBI progressions occurred. One deep vein thrombosis occurred in the placebo arm. CONCLUSION: TBI progression rates after starting enoxaparin in small, stable injuries 24 hours after injury are similar to those of placebo and are subclinical. The next Delayed Versus Early Enoxaparin Prophylaxis studies will assess efficacy of this practice in a powered study on the low-risk arm and a pilot trial of safety of a 72-hour time point in the moderate-risk arm. LEVEL OF EVIDENCE: Therapeutic study, level II.

Original languageEnglish (US)
Pages (from-to)1434-1441
Number of pages8
JournalJournal of Trauma and Acute Care Surgery
Volume73
Issue number6
DOIs
StatePublished - Dec 2012

Fingerprint

Enoxaparin
Placebos
Wounds and Injuries
Venous Thromboembolism
Confidence Intervals
Traumatic Brain Injury
Therapeutics
Double-Blind Method
Venous Thrombosis
Anticoagulants
Randomized Controlled Trials
Tomography
Safety

Keywords

  • Brain injury
  • enoxaparin
  • prophylaxis
  • randomized trial
  • venous thromboembolism

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Surgery

Cite this

@article{65771439dc0a47a0a30df7baf8ce2de6,
title = "A randomized, double-blinded, placebo-controlled pilot trial of anticoagulation in low-risk traumatic brain injury: The Delayed Versus Early Enoxaparin Prophylaxis i (DEEP I) study",
abstract = "BACKGROUND: Our group has created an algorithm for venous thromboembolism prophylaxis after traumatic brain injury (TBI), which stratifies patients into low, moderate, and high risk for spontaneous injury progression and tailors a prophylaxis regimen to each arm. We present the results of the Delayed Versus Early Enoxaparin Prophylaxis I study, a double-blind, placebo-controlled, randomized pilot trial on the low-risk arm. METHODS: In this two-institution study, patients presenting within 6 hours of injury with prespecified small TBI patterns and stable scans at 24 hours after injury were randomized to receive enoxaparin 30 mg bid or placebo from 24 to 96 hours after injury in a double-blind fashion. An additional computed tomography scan was obtained on all subjects 24 hours after starting treatment (and therefore 48 hours after injury). The primary end point was the radiographic worsening of TBI; secondary end points were venous thromboembolism occurrence and extracranial hemorrhagic complications. RESULTS: A total of 683 consecutive patients with TBI were screened during the 28 center months. The most common exclusions were for injuries larger than the prespecified criteria (n = 199) and preinjury anticoagulant use (n = 138). Sixty-two patients were randomized to enoxaparin (n = 34) or placebo (n = 28). Subclinical, radiographic TBI progression rates on the scans performed 48 hours after injury and 24 hours after start of treatment were 5.9{\%} (95{\%} confidence interval [CI], 0.7-19.7{\%}) for enoxaparin and 3.6{\%} (95{\%} CI, 0.1-18.3{\%}) for placebo, a treatment effect difference of 2.3{\%} (95{\%} CI, -14.42-16.5{\%}). No clinical TBI progressions occurred. One deep vein thrombosis occurred in the placebo arm. CONCLUSION: TBI progression rates after starting enoxaparin in small, stable injuries 24 hours after injury are similar to those of placebo and are subclinical. The next Delayed Versus Early Enoxaparin Prophylaxis studies will assess efficacy of this practice in a powered study on the low-risk arm and a pilot trial of safety of a 72-hour time point in the moderate-risk arm. LEVEL OF EVIDENCE: Therapeutic study, level II.",
keywords = "Brain injury, enoxaparin, prophylaxis, randomized trial, venous thromboembolism",
author = "Herbert Phelan and Wolf, {Steven E} and Norwood, {Scott H.} and Kim Aldy and Brakenridge, {Scott C.} and Alexander Eastman and Madden, {Christopher J} and Nakonezny, {Paul A} and Lisa Yang and Chason, {David P} and Arbique, {Gary M} and John Berne and Minei, {Joseph P}",
year = "2012",
month = "12",
doi = "10.1097/TA.0b013e31825ac49e",
language = "English (US)",
volume = "73",
pages = "1434--1441",
journal = "Journal of Trauma and Acute Care Surgery",
issn = "2163-0755",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - A randomized, double-blinded, placebo-controlled pilot trial of anticoagulation in low-risk traumatic brain injury

T2 - The Delayed Versus Early Enoxaparin Prophylaxis i (DEEP I) study

AU - Phelan, Herbert

AU - Wolf, Steven E

AU - Norwood, Scott H.

AU - Aldy, Kim

AU - Brakenridge, Scott C.

AU - Eastman, Alexander

AU - Madden, Christopher J

AU - Nakonezny, Paul A

AU - Yang, Lisa

AU - Chason, David P

AU - Arbique, Gary M

AU - Berne, John

AU - Minei, Joseph P

PY - 2012/12

Y1 - 2012/12

N2 - BACKGROUND: Our group has created an algorithm for venous thromboembolism prophylaxis after traumatic brain injury (TBI), which stratifies patients into low, moderate, and high risk for spontaneous injury progression and tailors a prophylaxis regimen to each arm. We present the results of the Delayed Versus Early Enoxaparin Prophylaxis I study, a double-blind, placebo-controlled, randomized pilot trial on the low-risk arm. METHODS: In this two-institution study, patients presenting within 6 hours of injury with prespecified small TBI patterns and stable scans at 24 hours after injury were randomized to receive enoxaparin 30 mg bid or placebo from 24 to 96 hours after injury in a double-blind fashion. An additional computed tomography scan was obtained on all subjects 24 hours after starting treatment (and therefore 48 hours after injury). The primary end point was the radiographic worsening of TBI; secondary end points were venous thromboembolism occurrence and extracranial hemorrhagic complications. RESULTS: A total of 683 consecutive patients with TBI were screened during the 28 center months. The most common exclusions were for injuries larger than the prespecified criteria (n = 199) and preinjury anticoagulant use (n = 138). Sixty-two patients were randomized to enoxaparin (n = 34) or placebo (n = 28). Subclinical, radiographic TBI progression rates on the scans performed 48 hours after injury and 24 hours after start of treatment were 5.9% (95% confidence interval [CI], 0.7-19.7%) for enoxaparin and 3.6% (95% CI, 0.1-18.3%) for placebo, a treatment effect difference of 2.3% (95% CI, -14.42-16.5%). No clinical TBI progressions occurred. One deep vein thrombosis occurred in the placebo arm. CONCLUSION: TBI progression rates after starting enoxaparin in small, stable injuries 24 hours after injury are similar to those of placebo and are subclinical. The next Delayed Versus Early Enoxaparin Prophylaxis studies will assess efficacy of this practice in a powered study on the low-risk arm and a pilot trial of safety of a 72-hour time point in the moderate-risk arm. LEVEL OF EVIDENCE: Therapeutic study, level II.

AB - BACKGROUND: Our group has created an algorithm for venous thromboembolism prophylaxis after traumatic brain injury (TBI), which stratifies patients into low, moderate, and high risk for spontaneous injury progression and tailors a prophylaxis regimen to each arm. We present the results of the Delayed Versus Early Enoxaparin Prophylaxis I study, a double-blind, placebo-controlled, randomized pilot trial on the low-risk arm. METHODS: In this two-institution study, patients presenting within 6 hours of injury with prespecified small TBI patterns and stable scans at 24 hours after injury were randomized to receive enoxaparin 30 mg bid or placebo from 24 to 96 hours after injury in a double-blind fashion. An additional computed tomography scan was obtained on all subjects 24 hours after starting treatment (and therefore 48 hours after injury). The primary end point was the radiographic worsening of TBI; secondary end points were venous thromboembolism occurrence and extracranial hemorrhagic complications. RESULTS: A total of 683 consecutive patients with TBI were screened during the 28 center months. The most common exclusions were for injuries larger than the prespecified criteria (n = 199) and preinjury anticoagulant use (n = 138). Sixty-two patients were randomized to enoxaparin (n = 34) or placebo (n = 28). Subclinical, radiographic TBI progression rates on the scans performed 48 hours after injury and 24 hours after start of treatment were 5.9% (95% confidence interval [CI], 0.7-19.7%) for enoxaparin and 3.6% (95% CI, 0.1-18.3%) for placebo, a treatment effect difference of 2.3% (95% CI, -14.42-16.5%). No clinical TBI progressions occurred. One deep vein thrombosis occurred in the placebo arm. CONCLUSION: TBI progression rates after starting enoxaparin in small, stable injuries 24 hours after injury are similar to those of placebo and are subclinical. The next Delayed Versus Early Enoxaparin Prophylaxis studies will assess efficacy of this practice in a powered study on the low-risk arm and a pilot trial of safety of a 72-hour time point in the moderate-risk arm. LEVEL OF EVIDENCE: Therapeutic study, level II.

KW - Brain injury

KW - enoxaparin

KW - prophylaxis

KW - randomized trial

KW - venous thromboembolism

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DO - 10.1097/TA.0b013e31825ac49e

M3 - Article

VL - 73

SP - 1434

EP - 1441

JO - Journal of Trauma and Acute Care Surgery

JF - Journal of Trauma and Acute Care Surgery

SN - 2163-0755

IS - 6

ER -