Assessment of the Anti-inflammatory Effect of Heparin Infusion Versus Subcutaneous Injection in Septic Patients

NCT04313790 | Completed Phase 2

• 1 other identifier: IVSCHEP
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep venous thrombosis (DVT), is a common and severe complication of critical illness. Critically ill patients are at high risk of VTE because they combine both general risk factors together with specific ICU risk factors of VTE. Vasopressor administration was found to be an independent risk factor for DVT. certainly explained by reduced absorption of subcutaneous heparin linked to the vasoconstriction of peripheral blood vessels. For critically ill patients, due to the altered pharmacokinetics behavior of unfractionated heparin, continuous intravenous infusion of the low doses of unfractionated heparin has been proposed. Standard prophylaxis with subcutaneous (SC) heparin is less efficient in patients requiring vasopressors. Sepsis is a systemic inflammatory response due to an infection. Both inflammatory mediators and coagulation are involved in sepsis. the release of inflammatory mediators such as interleukins and tumor necrosis factor causes damage to the endothelium and activation of coagulation which promotes the inflammatory process. Unfractionated heparin is the most negatively charged biological molecule known, heparin has a strong ability to interfere with the functioning of positively charged molecules. Due to the difference in charges, heparin has been documented to interact with over 100 proteins.57 Interleukins, cytokines, and receptors located on endothelial cells, which are involved in the acute phase response, are positively charged and thus are a reasonable target for the modulating effects of heparin. Heparin has strong anti-inflammatory effects with many possible mechanisms, including binding to cell-surface glycosaminoglycans, preventing leukocyte migration, direct binding to chemokines and cytokines, and inhibition of intracellular NF-kB.

Conditions

Sepsis; Critical Illness

Keywords

heparin infusion; DVT prophylaxis; Anti inflammatory

Outcome Measures

Primary Outcomes (2)

• Dynamic changes of HBP

  Measuring the differences of HBP dynamic changes between the two study groups

  day one, two, and seven

• Dynamic changes of PAL-1

  Measuring the differences of PAL-1 dynamic changes between the two study groups

  day one, two, and seven

Study Arms (2)

Heparin Infusion

EXPERIMENTAL

heparin infusion 500unit \\hour

Drug: Heparin Infusion

Subcutaneus Heparin

OTHER

subcutaneous heparin 5000unit \\ 8 hours

Other: subcutaneous heparin

Interventions

Heparin Infusion DRUG

500 unit heparin infusion \\ hour for DVT prophylaxis experimental group (n=20)

Also known as: new regimen

Heparin Infusion

subcutaneous heparin OTHER

5000 unit subcutaneous heparin /8 hours control group n=(20)

Also known as: conventional regimen

Subcutaneus Heparin

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adults Patients aged 18 years old or greatecritically ill patients aged 18-65 years diagnosed with sepsis/septic shock or developed sepsis/septic shock during their ICU length of stay were enrolled.

You may not qualify if:

• Thrombocytopenia, Intracerebral hemorrhage at the time of sepsis Bleeding tendency (INR ≥ 1.5 or PLT \< 50 x 109/L,) Medical condition requiring therapeutic anticoagulation Age \< 18 years Previous history of Heparin Induced Thrombocytopenia (HIT).

Sponsors & Collaborators

• Damanhour University: lead

Study Sites (1)

amira Bisher kassem

Damanhūr Shubrā, 22511, Egypt

Location

Related Publications (13)

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  PMID: 16003063 BACKGROUND

• Dorffler-Melly J, de Jonge E, Pont AC, Meijers J, Vroom MB, Buller HR, Levi M. Bioavailability of subcutaneous low-molecular-weight heparin to patients on vasopressors. Lancet. 2002 Mar 9;359(9309):849-50. doi: 10.1016/s0140-6736(02)07920-5.

  PMID: 11897286 BACKGROUND

• Selby R, Geerts W. Prevention of venous thromboembolism: consensus, controversies, and challenges. Hematology Am Soc Hematol Educ Program. 2009:286-92. doi: 10.1182/asheducation-2009.1.286.

  PMID: 20008212 BACKGROUND

• Hirsh J, Raschke R. Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):188S-203S. doi: 10.1378/chest.126.3_suppl.188S.

  PMID: 15383472 BACKGROUND

• Jaimes F, De La Rosa G, Morales C, Fortich F, Arango C, Aguirre D, Munoz A. Unfractioned heparin for treatment of sepsis: A randomized clinical trial (The HETRASE Study). Crit Care Med. 2009 Apr;37(4):1185-96. doi: 10.1097/CCM.0b013e31819c06bc.

  PMID: 19242322 BACKGROUND

• Wang C, Chi C, Guo L, Wang X, Guo L, Sun J, Sun B, Liu S, Chang X, Li E. Heparin therapy reduces 28-day mortality in adult severe sepsis patients: a systematic review and meta-analysis. Crit Care. 2014 Oct 16;18(5):563. doi: 10.1186/s13054-014-0563-4.

  PMID: 25318353 BACKGROUND

• Lorente L, Martin MM, Borreguero-Leon JM, Sole-Violan J, Ferreres J, Labarta L, Diaz C, Jimenez A, Paramo JA. Sustained high plasma plasminogen activator inhibitor-1 levels are associated with severity and mortality in septic patients. Thromb Res. 2014 Jul;134(1):182-6. doi: 10.1016/j.thromres.2014.04.013. Epub 2014 Apr 29.

  PMID: 24814968 BACKGROUND

• Elsayed E, Becker RC. The impact of heparin compounds on cellular inflammatory responses: a construct for future investigation and pharmaceutical development. J Thromb Thrombolysis. 2003 Feb;15(1):11-8. doi: 10.1023/a:1026184100030.

  PMID: 14574071 BACKGROUND

• Li L, Pian Y, Chen S, Hao H, Zheng Y, Zhu L, Xu B, Liu K, Li M, Jiang H, Jiang Y. Phenol-soluble modulin alpha4 mediates Staphylococcus aureus-associated vascular leakage by stimulating heparin-binding protein release from neutrophils. Sci Rep. 2016 Jul 7;6:29373. doi: 10.1038/srep29373.

  PMID: 27383625 BACKGROUND

• Chen S, Xie W, Wu K, Li P, Ren Z, Li L, Yuan Y, Zhang C, Zheng Y, Lv Q, Jiang H, Jiang Y. Suilysin Stimulates the Release of Heparin Binding Protein from Neutrophils and Increases Vascular Permeability in Mice. Front Microbiol. 2016 Aug 26;7:1338. doi: 10.3389/fmicb.2016.01338. eCollection 2016.

  PMID: 27617009 BACKGROUND

• Tyden J, Herwald H, Hultin M, Wallden J, Johansson J. Heparin-binding protein as a biomarker of acute kidney injury in critical illness. Acta Anaesthesiol Scand. 2017 Aug;61(7):797-803. doi: 10.1111/aas.12913. Epub 2017 Jun 5.

  PMID: 28585315 BACKGROUND

• Fisher J, Russell JA, Bentzer P, Parsons D, Secchia S, Morgelin M, Walley KR, Boyd JH, Linder A. Heparin-Binding Protein (HBP): A Causative Marker and Potential Target for Heparin Treatment of Human Sepsis-Induced Acute Kidney Injury. Shock. 2017 Sep;48(3):313-320. doi: 10.1097/SHK.0000000000000862.

  PMID: 28319494 BACKGROUND

• Lin Q, Shen J, Shen L, Zhang Z, Fu F. Increased plasma levels of heparin-binding protein in patients with acute respiratory distress syndrome. Crit Care. 2013 Jul 24;17(4):R155. doi: 10.1186/cc12834.

  PMID: 23883488 BACKGROUND

MeSH Terms

Conditions

Sepsis; Critical Illness

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Study Officials

• Ahmed M Salahuddin, PHD

  Damanhour University

  STUDY DIRECTOR

• Aymen A Eltayar, MD

  Damanhour Teatching Hospital

  STUDY DIRECTOR

• Noha A El Bassiouny, PHD

  Damanhour University

  STUDY CHAIR

• Amira B Kassem, PHD

  Damanhour University

  STUDY CHAIR

• Nouran A Elsheikh, Pharm-D

  Damanhour Teaching Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: single (Participant)
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized Control Trial

Study Record Dates

• First Submitted: March 9, 2020
• First Posted: March 18, 2020
• Study Start: August 29, 2020
• Primary Completion: October 11, 2022
• Study Completion: October 11, 2022
• Last Updated: July 19, 2023

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)