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Streptokinase Versus Unfractionated Heparin Nebulization in Severe ARDS

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03465085
Recruitment Status : Completed
First Posted : March 14, 2018
Last Update Posted : March 14, 2018
Sponsor:
Information provided by (Responsible Party):
Ahmed Abdelaal Ahmed Mahmoud, Beni-Suef University

Brief Summary:

Background: Intra-alveolar clotting and alveolar collapse in ARDS is due to alveolar capillaries epithelial and leakage. Subsequently, collapse induces hypoxemia that is resistant to recruitment (RM). Heparin and Streptokinase may prevent or dissolve intra-alveolar fibrin clot respectively helping alveolar re-expansion. We examined and compared the effect of nebulizing Heparin versus Streptokinase on reversing this pathology.

Methods: Sixty severe ARDS (PaO2/FiO2<100) patients and failure of RM, prone position (PP) and neuromuscular block (NMB) were partially randomised into Group (I): (n=20) received nebulized Heparin 10000 IU/4h. Group (II): (n=20) received nebulized Streptokinase 250,000 IU/4h. Group (III): (n=20) received conservative management. Randomization to either Heparin or Streptokinase groups was applied to patients whom guardian accepted participation, while those who declined participation were followed-up as a control. The primary outcome was the change in PaO2/FiO2; the secondary outcomes included the change in compliance, plateau pressure, ventilation-off days, coagulation and ICU mortality.


Condition or disease Intervention/treatment Phase
Acute Respiratory Distress Syndrome Severe Acute Respiratory Syndrome Drug: Unfractionated heparin Drug: Streptokinase Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Intervention Model Description:

Group (I): Heparin group (n=20) received nebulized Heparin 10000 IU/4h. Group (II): Streptokinase group (n=20) received nebulized Streptokinase 250,000 IU/4h.

Group (III): Control group (n=20) received conservative management

Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Masking Description: Investigators prepared and administered the study medication. participants, ICU physician and nurses, and the outcomes assessor were blinded to the two randomized groups
Primary Purpose: Treatment
Official Title: Streptokinase Versus Unfractionated Heparin Nebulization in Patients With Severe Acute Respiratory Distress Syndrome (ARDS): A Partially Randomized Controlled Trial
Actual Study Start Date : February 18, 2016
Actual Primary Completion Date : January 30, 2018
Actual Study Completion Date : January 30, 2018


Arm Intervention/treatment
Experimental: Group I: Heparin nebulized group
Group (I): 20 patients received inhaled Unfractionated Heparin at a dose of 10000 IU/4h by nebulizer, with the total daily dose of nebulized Unfractionated Heparin 60,000 IU
Drug: Unfractionated heparin
Heparin or Streptokinase were nebulized by Aeroneb Pro@ Lab mesh nebulizer (Aerogen Limited, Galway, Ireland) which is incorporated within GE Healthcare's Engström Carestation ventilator (General Electric Company, Finland). Aeroneb nebulizer is a palladium vibrating mesh nebulizer. The central aperture plate of the nebulizer is 5mm in diameter and is perforated with 1000 precision formed holes, that vibrate at 128,000 times per second, to produce the particles with size 1-5 micron in diameter with average MMAD (Mean Mass Aerodynamic Diameter) is 2.1 microns. The nebulized medication (either streptokinase 250,000 IU or heparin 10.000 IU) was prepared in 3 ml volume of distilled water and nebulized for a period of 15 minutes every 4 hours.
Other Name: Heparin-Sodium Injection 5.000 I.U./ml (B BRAUN)

Experimental: Group II: Streptokinase group
Group (II): 20 patients received inhaled Streptokinase at a dose of 250,000 IU/4h by nebulizer, with the total daily dose of nebulized Streptokinase 1,500,000 IU.
Drug: Streptokinase
Heparin or Streptokinase were nebulized by Aeroneb Pro@ Lab mesh nebulizer (Aerogen Limited, Galway, Ireland) which is incorporated within GE Healthcare's Engström Carestation ventilator (General Electric Company, Finland). Aeroneb nebulizer is a palladium vibrating mesh nebulizer. The central aperture plate of the nebulizer is 5mm in diameter and is perforated with 1000 precision formed holes, that vibrate at 128,000 times per second, to produce the particles with size 1-5 micron in diameter with average MMAD (Mean Mass Aerodynamic Diameter) is 2.1 microns. The nebulized medication (either streptokinase 250,000 IU or heparin 10.000 IU) was prepared in 3 ml volume of distilled water and nebulized for a period of 15 minutes every 4 hours.
Other Name: Streptase (Aventis Behring GmbH, Marburg, Germany U.S)

No Intervention: Group III: Control group
Twenty patients whom guardian declined to participate actively in the study but accepted to participate passively by consenting for using their data were assigned as Group III or the control group and received conservative management



Primary Outcome Measures :
  1. Change in PaO2/FiO2 ratio [ Time Frame: daily over eight days ]
    Change in the ratio of arterial oxygen tension to fraction of inspired oxygen from the baseline (day 0, before randomization and or the start of intervention) to day 1 to day 8 after the randomization and or start of intervention.


Secondary Outcome Measures :
  1. Change in the plateau pressure [ Time Frame: daily over eight days ]
    Change in the plateau airway pressure during ventilation from the baseline (day 0, before randomization and or the start of intervention) to day 1 to day 8 after the randomization and or start of intervention.

  2. Change in the pulmonary compliance [ Time Frame: daily over eight days ]
    change in volume of the lungs per change in pressure during ventilation from the baseline (day 0, before randomization and or the start of intervention) to day 1 to day 8 after the randomization and or start of intervention.

  3. ICU survival rate [ Time Frame: At the end of ICU stay up to one year after the start of recruitment ]
    Number of patients who are discharged alive

  4. ICU length of stay [ Time Frame: At the end of ICU stay up to one year after the start of recruitment ]
    the total duration the patient stays in ICU

  5. Tracheostomy rate [ Time Frame: During ICU stay up to one month after the start of recruitment ]
    number of patients who required tracheostomy



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Ages Eligible for Study:   21 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Severe ARDS with PO2/FiO2 ratio<100.
  • Failure of Recruitment Maneuver (RM), Prone Position (PP) or Neuro-Muscular Block (NMB) to improve hypoxemia.
  • No contraindications to thrombolytic or anticoagulant therapy (e.g. Coagulopathy, Heparin-Induced Thrombocytopenia, Previous administration of streptokinase, Known or suspected allergy to heparin or streptokinase, History of intracranial hemorrhage in the past 12 months, Patients with an epidural catheter in place or likely to be placed within the next 48 h.).
  • Static compliance <50 ml/cmH2O

Exclusion Criteria:

  • PO2/FiO2 ratio>100.
  • The success of Recruitment Maneuver (RM), Prone Position (PP) or Neuro-Muscular Block (NMB) to improve hypoxemia.
  • Contraindications to thrombolytic or anticoagulant therapy (e.g. Coagulopathy, Heparin-Induced Thrombocytopenia, Previous administration of streptokinase, Known or suspected allergy to heparin or streptokinase, History of intracranial hemorrhage in the past 12 months, Patients with an epidural catheter in place or likely to be placed within the next 48 h.)
  • Static compliance >50 ml/cmH2O

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03465085


Sponsors and Collaborators
Beni-Suef University
Investigators
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Study Director: Hatem Hatem Elmoutaz Mahmoud, MD Beni-Suef University
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Responsible Party: Ahmed Abdelaal Ahmed Mahmoud, Associate Professor of Anesthesiology, Beni-Suef University
ClinicalTrials.gov Identifier: NCT03465085    
Other Study ID Numbers: Heparin-Streptokinase-ARDS
First Posted: March 14, 2018    Key Record Dates
Last Update Posted: March 14, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ahmed Abdelaal Ahmed Mahmoud, Beni-Suef University:
ARDS
Streptokinase
Heparin
Nebulization
Inhaled Thrombolytics
Inhaled Anticoagulation
Additional relevant MeSH terms:
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Severe Acute Respiratory Syndrome
Coronavirus Infections
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Syndrome
Disease
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Heparin
Calcium heparin
Streptokinase
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action