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PGE1 as Additive Anticoagulant in ECMO-Therapy (ECMO_PGE1)

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ClinicalTrials.gov Identifier: NCT02895373
Recruitment Status : Recruiting
First Posted : September 9, 2016
Last Update Posted : August 17, 2018
Sponsor:
Information provided by (Responsible Party):
Thomas Staudinger, Medical University of Vienna

Brief Summary:
Bleeding complications and thromboembolic complications are frequent during extracorporeal membrane oxygenation (ECMO). Retrospective data suggest that platelet inhibition using prostaglandins, in this case PGE1, may reduce thromboembolic complications without increasing the bleeding risk. This randomized, double-blind trial aims to investigate the effects of PGE1 on bleeding risk, thromboembolic complications and the function of the ECMO.

Condition or disease Intervention/treatment Phase
Respiratory Distress Syndrome, Adult Extracorporeal Membrane Oxygenation Drug: Alprostadil Drug: 0.9% sodium chloride solution Phase 2

Detailed Description:

Prostaglandins may inhibit platelet activation via the P2Y1 ADP receptor. Platelets may contribute to thromboembolic complications and coagulation activation during ECMO therapy. Retrospective data suggest that treatment with PGE1 may serve beneficial by reducing the amount of heparin needed for inhibition of coagulation activation, and by reducing the thromboembolic risk without increasing the risk of bleeding.

Inhibition of platelets via PGE1 (Alprostadil) may be interesting in this setting, because, in contrast to other platelet inhibitors, it has a very short half-life and platelets remain susceptible for activation by more potent agonists (i.e. thrombin, ADP). Thus, although reducing the contribution of platelets to coagulation activation, it may not affect safety of participating subjects.

This randomized, double-blind, placebo controlled trial will investigate whether treatment of patients with ECMO therapy proves beneficial.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 114 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Prospective Randomized, Double Blind Study on Safety and Efficacy of Alprostadil as Additional Anticoagulant in Patients With Veno- Venous Extracorporeal Membrane Oxygenation (ECMO)
Study Start Date : July 2016
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : October 2019


Arm Intervention/treatment
Experimental: Alprostadil
heparin (dose adjusted to aptt 50-60s) + Alprostadil (=PGE1) 5ng/kg/min, continuously, start within 24h of initiation of ECMO therapy and end at the end of ECMO therapy
Drug: Alprostadil
5ng/kg/min, continuously, start within 24h of initiation of ECMO therapy and end at the end of ECMO therapy

Placebo Comparator: Placebo
heparin (dose adjusted to aptt 50-60s) + 0.9% sodium chloride infusion, continuously, start within 24h of initiation of ECMO therapy and end at the end of ECMO therapy
Drug: 0.9% sodium chloride solution
continuously, start within 24h of initiation of ECMO therapy and end at the end of ECMO therapy




Primary Outcome Measures :
  1. Bleeding rate (quantified by the number of packed red blood cells transfused in relation to the duration of ECMO therapy) [ Time Frame: up to 6 months ]
    The bleeding rate will be quantified by the number of packed red blood cells in relation to the duration of ECMO therapy. This duration may vary and cannot be predicted. Thus, we will calculate the required number of packed red blood cells i.e. per week.


Secondary Outcome Measures :
  1. number of bleeding incidences and severity of bleeding (bleeding grades) [ Time Frame: up to six months ]

    type 0: no bleeding type1: bleeding that is not actionable type 2: any overt actionable sign of hemorrhage type3: a) overt bleeding plut hb drop of 3-5g/dl b) >5g/dl, cardiac tamponade, requiring surgical intervention, bleeding requiring vasoactive agents c)intracranial bleeding, type 5: fatal bleeding

    number and severity of bleeding relative to the duration of ECMO therapy


  2. Number of Clotting Events [ Time Frame: up to six months ]
    • clinically noticeable thromboembolic events
    • cannulized veins (Duplex 24h after canula removal)
    • need of Membrane- changes,, macroscopic thrombus, discoloration
    • Global clotting tests (prothrombin time, activated partial thromboplastin time, Fibrinogen, D-Dimer)

    number of Clotting events in relation to the duration of ECMO therapy.


  3. Function of the membrane oxygenator [ Time Frame: up to six months ]
    The function of the membrane oxygenator will be assessed on a daily basis as part of clinical routine.This includes the capacity of oxygen transfer and carbon-dioxide (CO2) transfer.

  4. Number of changes of the membrane oxygenator relative to the duration of ECMO therapy [ Time Frame: up to six months ]
    Membrane oxygenators need to be changed due to loss of function (cause by clotting etc.).

  5. Inflammation specific biomarkers (i.e. C-reactive protein, blood counts, reticulated platelets, etc.) [ Time Frame: Time points: Immediately prior to initiation of ECMO, 24, 48 and 72h after initiation of ECMO, then twice a week until end of ECMO therapy, up to 12 months ]
    daily routine measurements and frozen plasma

  6. Global Coagulation assays [ Time Frame: Time points: Immediately prior to initiation of ECMO, 24, 48 and 72h after initiation of ECMO, then twice a week until end of ECMO therapy, up to 12 months ]
  7. Thromboelastometry [ Time Frame: Time points: Immediately prior to initiation of ECMO, 24, 48 and 72h after initiation of ECMO, then twice a week until end of ECMO therapy, up to 12 months ]
  8. platelet function analyzer-100 [ Time Frame: Time points: Immediately prior to initiation of ECMO, 24, 48 and 72h after initiation of ECMO, then twice a week until end of ECMO therapy, up to 12 months ]
  9. Fibrinogen levels [ Time Frame: Time points: Immediately prior to initiation of ECMO, 24, 48 and 72h after initiation of ECMO, then twice a week until end of ECMO therapy, up to 12 months ]
  10. whole blood aggregometry [ Time Frame: Time points: Immediately prior to initiation of ECMO, 24, 48 and 72h after initiation of ECMO, then twice a week until end of ECMO therapy, up to 12 months ]
  11. D-Dimer levels [ Time Frame: Time points: Immediately prior to initiation of ECMO, 24, 48 and 72h after initiation of ECMO, then twice a week until end of ECMO therapy, up to 12 months ]
  12. Catecholamines [ Time Frame: Time points: Immediately prior to initiation of ECMO, 24, 48 and 72h after initiation of ECMO, then twice a week until end of ECMO therapy, up to 12 months ]
    need for and dose of catecholamines

  13. cardiac output [ Time Frame: Time points: Immediately prior to initiation of ECMO, 24, 48 and 72h after initiation of ECMO, then twice a week until end of ECMO therapy, up to 12 months ]
  14. blood pressure [ Time Frame: Time points: Immediately prior to initiation of ECMO, 24, 48 and 72h after initiation of ECMO, then twice a week until end of ECMO therapy, up to 12 months ]
  15. mortality [ Time Frame: Day 28/90, ICU mortality assessed at the discharge from the Intensive Care unit, this will be up to 12 months after inclusion into the study ]
    by chart review or telephone call

  16. number of platelet transfusions, fresh frozen plamsa, coagulation interventions etc. [ Time Frame: up to six months ]
    by chart review, number relative to the duration of ECMO therapy

  17. number of platelet transfusions [ Time Frame: up to six months ]
    by chart review, number relative to the duration of ECMO therapy

  18. number of coagulation interventions [ Time Frame: up to six months ]
    by chart review, number relative to the duration of ECMO therapy



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • minimum age 18 years

    • Veno-Venous- ECMO
    • Minimum of 24h planned ECMO- therapy

Exclusion Criteria:

  • • Long- term therapy with other antiplatelet drugs including Acetyl Salicylic Acid

    • known Heparin induced thrombocytopenia
    • Bleeding diathesis = contraindication for heparin (e.g. GI-bleeding, Intracerebral bleeding)
    • Platelets < 50 G/L
    • Thromboplastin time < 50%
    • Pregnancy
    • Patient < 18 years
    • prothrombin time <50%

Drop out criteria:

  • Major bleeding (from Type 3 bleeding; see "primary objective")
  • Occurrence of HIT (4 T- Score: Number of platelets, development over time, manifestation of thrombosis, other reasons for thrombocytopenia [10])
  • Plt < 50 G/l

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): NCT02895373


Contacts
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Contact: Thomas Staudinger, MD +43 1 40400 ext 44920 thomas.staudinger@meduniwien.ac.at
Contact: Katharina Riss, MD +43 1 40400 ext 44920 katharina.riss@meduniwien.ac.at

Locations
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Austria
Medical University of Vienna, Department of Medicine I, Intensive Care Unit Recruiting
Vienna, Austria, 1090
Contact: Thomas Staudinger, MD    +43 1 40400 ext 44920    thomas.staudinger@meduniwien.ac.at   
Contact: Katharina Riss, MD    +43 1 40400 ext 44920    katharina.riss@meduniwien.ac.at   
Sub-Investigator: Christian Schoergenhofer, MD         
Principal Investigator: Thomas Staudinger, MD         
Sub-Investigator: Katharina Riss, MD         
Sub-Investigator: Bernd Jilma, MD         
Sub-Investigator: Peter Schellongowski, MD         
Sub-Investigator: Andja Bojic, MD         
Sponsors and Collaborators
Thomas Staudinger
Investigators
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Principal Investigator: Thomas Staudinger, MD Medical University of Vienna

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Responsible Party: Thomas Staudinger, Ao.Univ.Prof. Dr. med, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT02895373     History of Changes
Other Study ID Numbers: ECMO_PGE1_2.1
First Posted: September 9, 2016    Key Record Dates
Last Update Posted: August 17, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Data will be published in a peer-reviewed journal, individual data will not be made publicly available except by a direct request to the PI (in an anonymized fashion)

Keywords provided by Thomas Staudinger, Medical University of Vienna:
platelet inhibition
alprostadil
extracorporeal membrane oxygenation
bleeding
thromboembolic

Additional relevant MeSH terms:
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Anticoagulants
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury
Alprostadil
Platelet Aggregation Inhibitors
Vasodilator Agents
Urological Agents