Assessment of Pleotropic Effect of Heparin Infusion Versus Subcutaneous Injection in Septic Shock Patients

Sponsor

Damanhour University (Other)

Overall Status

Unknown status

CT.gov ID

NCT04313790

Collaborator

(none)

100

Enrollment

Location

Arms

Anticipated Duration (Months)

16.6

Patients Per Site Per Month

Study Details

Study Description

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. Critically ill patients, due to 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 the inflammatory mediators such as interleukins and tumor necrosis factor cause damage of the endothelium and activation of coagulation which promotes 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 glycosaminoglycan's, preventing leukocyte migration, direct binding to chemokines and cytokines, and inhibition of intracellular NF-kB .

Condition or Disease	Intervention/Treatment	Phase
Septic Shock Critical Illness	Drug: Heparin Infusion Other: subcutaneous heparin	Phase 2

Detailed Description

Ethical committee approval will be obtained from Ethics committee of Faculty of Pharmacy, Damanhour University.
All participants or their next kin should agree to participate in this clinical study and will provide informed consent.
100 participants who are critically ill with septic shock.
The 100 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

All patients will be subjected directly at time of enrollment to the following:

Full patient history and clinical examination.
complete blood picture, liver function tests, renal function tests.
The initial cause of ICU admission and define the origin of 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).

All patients will be monitored for the incidence of DVT, minor and major bleeding during their intensive care unit stay (ICU).
Coagulation profile, serum lactate, serum electrolytes, hypoxic index,28-day mortality and the following pro inflammatory biomarkers will be measured at the start and at day 2 of the study.

CRP ii. Heparin binding protein (HBP) iii. IL-6 iv. Neutrophil gelatinase -associated lipocalin (NGAL). v. Plasminogen activator inhibitor (PAI).

Patients demographic data will be recorded with respect to sex. age, weight, disease and medication history.
Statistical tests appropriate to the study design will be conducted to evaluate the significance of the results.
Results, conclusion, discussion and recommendations will be given.
A P value of less than 0.05 will be considered statistically significance.
Statistical analysis will be performed by STATA/IC (version 16 for Windows); Stata Corp LP, College Station, TX.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized Control TrialRandomized Control Trial

Masking:

Double (Participant, Care Provider)

Masking Description:

double(Participant,Care provider)

Primary Purpose:

Prevention

Official Title:

Assessment of Thrombo-prophylactic and Anti Inflammatory Effect of Unfractionated Heparin by Intravenous Infusion Versus Subcutaneous Injection in Critically Septic Shock Patients

Anticipated Study Start Date :

Jul 1, 2020

Anticipated Primary Completion Date :

Aug 24, 2020

Anticipated Study Completion Date :

Dec 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Heparin Infusion heparin infusion 500unit \hour	Drug: Heparin Infusion 500 unit heparin infusion \ hour for DVT prophylaxis experimental group (n=50) Other Names: new regimen
Other: Subcutaneus Heparin subcutaneous heparin 5000unit \ 8 hours	Other: subcutaneous heparin 5000 unit subcutaneous heparin /8 hours control group n=(50) Other Names: conventional regimen

Arm

Intervention/Treatment

Experimental: Heparin Infusion

heparin infusion 500unit \hour

Drug: Heparin Infusion

500 unit heparin infusion \ hour for DVT prophylaxis experimental group (n=50)

Other Names:

new regimen

Other: Subcutaneus Heparin

subcutaneous heparin 5000unit \ 8 hours

Other: subcutaneous heparin

5000 unit subcutaneous heparin /8 hours control group n=(50)

Other Names:

conventional regimen

Outcome Measures

Primary Outcome Measures

Venous thrombo-embolism [14 days]
Any occurrence of thromboembolism event
hypoxic index [7 days]
Arterial blood gases
Whole blood clotting time [7 days]
bedside clotting time measurement
28-days mortality [28 days]
All causes of mortality
lactic acid [5 days]
serum lactate
Vasopressor use [5 days]
Duration and dose of circulatory support
Activated partial prothrombin time [7 days]
measurement changes of activated partial prothrombin time

Secondary Outcome Measures

Heparin binding protein [8 hours]
plasma level of HBP
Plasminogen activator inhibitor (PAI) [2 days]
serum level of PAL
neutrophil gelatinase -associated lipocalin (NGAL). [7 days]
plasma NGAL
C-reactive protein [7 days]
plasma CRP

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 64 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adults Patients aged 18 years old or greater diagnosed with septic shock. The diagnosis of sepsis was made according to "surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock" by Sepsis-3 task force defines sepsis as the presence of suspected infection along with rise in total SOFA score ≥2 from baseline.