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SepsisPhase 2NCT04313790

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

A Phase 2 study testing Heparin Infusion and subcutaneous heparin in people with Sepsis and Critical Illness, run by Damanhour University at 1 site in Egypt.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 64 years
Conditions the study is for
Sepsis, Critical Illness
What is being tested?
Heparin Infusion and subcutaneous heparin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteEgypt
Study dates
29 Aug 2020to 11 Oct 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 64 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • -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).

Trial locations and contacts

1 site in 1 country.

Egypt1 site
  • amira Bisher kassem

    Damanhūr Shubrā, 22511

Other trials in Egypt

About this study

Official title: Assessment of the Anti-inflammatory Effect of Unfractionated Heparin Administered Either by Intravenous Infusion Versus Subcutaneous Injection in Critically Ill Septic Patients. A Randomized Controlled Trial

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.

Read the detailed description
  1. Ethical committee approval will be obtained from the Ethics Committee of the Faculty of Pharmacy, Damanhour University.
  2. All participants or their next kin should agree to participate in this clinical study and will provide informed consent.
  3. 40 participants who are critically ill with sepsis.
  4. The 40 participants will be randomly assigned into 2 groups:
  • Standard care group: will be treated with subcutaneous heparin 5000 units three times daily for DVT prophylaxis.
  • Experimental group: will be treated with heparin infusion 5000 unit\hour for DVT prophylaxis
  1. All patients will be subjected directly at the time of enrollment to the following:
  • Full patient history and clinical examination.
  • complete blood picture, liver function tests, and renal function tests.
  • The initial cause of ICU admission and define the origin of the present infection.
  • Complete cultures obtained urine, blood, and sputum.
  • Coagulation profile (prothrombin time, prothrombin activity, international normalization ratio (INR), clotting time, and activated partial thromboplastin time).
  • Arterial blood gases analysis (including hypoxic index).
  • The severity of disease assessment using Acute Physiology and Chronic Health Evaluation version II (APACHE II) score.
  • Organ failure assessment using Organ Failure Assessment (SOFA) score and quick (SOFA) score.
  • Kidney assessment using Kidney Disease Improving Global Outcomes (KDIGO) criteria.
  • Liver disease assessment using Child-Pugh Score.
  • Chest radiography, electrocardiography, and transthoracic echocardiography.
  • Vital signs (systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate temperature, blood sugar level, and urine output).
  1. All patients will be monitored for the incidence of DVT, minor and major bleeding during their intensive care unit stay (ICU).
  2. Coagulation profile, serum lactate, serum electrolytes, hypoxic index,14-day mortality, and the following pro-inflammatory biomarkers will be measured at the start and at days 1,2, and 7 of the study.
  3. CRP ii. Heparin-binding protein (HBP) iii. Plasminogen activator inhibitor (PAI).
  4. Patient demographic data will be recorded with respect to sex. age, weight, disease, and medication history.
  5. Statistical tests appropriate to the study design will be conducted to evaluate the significance of the results.
  6. Results, conclusion, discussion, and recommendations will be given.
  7. A p-value of less than 0.05 will be considered statistically significant.
  8. The study data were evaluated using IBM SPSS software (statistical product and service solution version 26.0)
Being tested
Heparin Infusion, subcutaneous heparin
Keywords
heparin infusion, DVT prophylaxis, Anti inflammatory
Medical subject headings
Sepsis, Critical Illness

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Heparin InfusionDrug

    Also called new regimen

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

  • subcutaneous heparinOther

    Also called conventional regimen

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

Study groups in NCT04313790
Study groupRoleWhat they receive
Heparin InfusionExperimentalheparin infusion 500unit \hour
Receives: Drug: Heparin Infusion
Subcutaneus HeparinOthersubcutaneous heparin 5000unit \ 8 hours
Receives: Other: subcutaneous heparin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dynamic changes of HBP

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

    Measured: day one, two, and seven

  2. Dynamic changes of PAL-1

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

    Measured: day one, two, and seven

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Mar 2020
  2. Study start29 Aug 2020
  3. Primary completion11 Oct 2022
  4. Study completion11 Oct 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized Control Trial
Masking
Single blind
Who is masked
Participant
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04313790
Sponsor's protocol ID
IVSCHEP
Status last verified
Mar 2020
First submitted
9 Mar 2020
Last updated
19 Jul 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Cook D, Crowther M, Meade M, Rabbat C, Griffith L, Schiff D, Geerts W, Guyatt G. Deep venous thrombosis in medical-surgical critically ill patients: prevalence, incidence, and risk factors. Crit Care Med. 2005 Jul;33(7):1565-71. doi: 10.1097/01.ccm.0000171207.95319.b2.

    PubMed 16003063
  • 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.

    PubMed 11897286
  • 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.

    PubMed 20008212
  • 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.

    PubMed 15383472
  • 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.

    PubMed 19242322
  • 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.

    PubMed 25318353
  • 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.

    PubMed 24814968
  • 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.

    PubMed 14574071
  • 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.

    PubMed 27383625
  • 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.

    PubMed 27617009
  • 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.

    PubMed 28585315
  • 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.

    PubMed 28319494
  • 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.

    PubMed 23883488

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Heparin Infusion and subcutaneous heparin in people with Sepsis and Critical Illness, run by Damanhour University at 1 site in Egypt.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dynamic changes of HBP (time frame: day one, two, and seven). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04313790, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2023.

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