Streptokinase Versus Unfractionated Heparin Nebulization in Severe ARDS

NCT03465085 | Completed Phase 3 DMC

• 1 other identifier: Heparin-Streptokinase-ARDS
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Acute Respiratory Distress Syndrome; Severe Acute Respiratory Syndrome

Keywords

ARDS; Streptokinase; Heparin; Nebulization; Inhaled Thrombolytics; Inhaled Anticoagulation

Outcome Measures

Primary Outcomes (1)

• Change in PaO2/FiO2 ratio

  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.

  daily over eight days

Secondary Outcomes (5)

• Change in the plateau pressure

  daily over eight days

• Change in the pulmonary compliance

  daily over eight days

• ICU survival rate

  At the end of ICU stay up to one year after the start of recruitment

• ICU length of stay

  At the end of ICU stay up to one year after the start of recruitment

• Tracheostomy rate

  During ICU stay up to one month after the start of recruitment

Study Arms (3)

Group I: Heparin nebulized group

EXPERIMENTAL

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

Group II: Streptokinase group

EXPERIMENTAL

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

Group III: Control group

NO INTERVENTION

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

Interventions

Unfractionated heparin DRUG

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.

Also known as: Heparin-Sodium Injection 5.000 I.U./ml (B BRAUN)

Group I: Heparin nebulized group

Streptokinase DRUG

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.

Also known as: Streptase (Aventis Behring GmbH, Marburg, Germany U.S)

Group II: Streptokinase group

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Beni-Suef University: lead

MeSH Terms

Conditions

Respiratory Distress Syndrome; Severe Acute Respiratory Syndrome

Interventions

Heparin; Streptokinase

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Respiratory Tract Infections; Infections; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Hatem Hatem Elmoutaz Mahmoud, MD

  Beni-Suef University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Investigators prepared and administered the study medication. participants, ICU physician and nurses, and the outcomes assessor were blinded to the two randomized groups
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Anesthesiology

Model Details: 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

Study Record Dates

• First Submitted: March 2, 2018
• First Posted: March 14, 2018
• Study Start: February 18, 2016
• Primary Completion: January 30, 2018
• Study Completion: January 30, 2018
• Last Updated: March 14, 2018

Record last verified: 2018-03