Respiratory Distress Syndrome, AdultPhase 2ECMO_PGE1NCT02895373
PGE1 as Additive Anticoagulant in ECMO-Therapy
A Phase 2 study testing Alprostadil and 0.9% sodium chloride solution in people with Respiratory Distress Syndrome, Adult and Extracorporeal Membrane Oxygenation, run by Thomas Staudinger at 1 site in Austria.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Respiratory Distress Syndrome, Adult, Extracorporeal Membrane Oxygenation
- What is being tested?
- Alprostadil and 0.9% sodium chloride solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteAustria
- Study dates
- Jul 2016to Jul 2021
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- minimum age 18 years
- Veno-Venous- ECMO
- Minimum of 24h planned ECMO- therapy
Who cannot join
- • 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Austria1 site
Medical University of Vienna, Department of Medicine I, Intensive Care Unit
Vienna, 1090
About this study
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)
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.
Read the 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.
- Being tested
- Alprostadil, 0.9% sodium chloride solution
- Keywords
- platelet inhibition, alprostadil, extracorporeal membrane oxygenation, bleeding, thromboembolic
- Medical subject headings
- Respiratory Distress Syndrome, Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlprostadilDrug
5ng/kg/min, continuously, start within 24h of initiation of ECMO therapy and end at the end of ECMO therapy
0.9% sodium chloride solutionDrug
continuously, start within 24h of initiation of ECMO therapy and end at the end of ECMO therapy
| Study group | Role | What they receive |
|---|---|---|
| Alprostadil | Experimental | 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 Receives: Drug: Alprostadil |
| Placebo | Placebo comparator | 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 Receives: Drug: 0.9% sodium chloride solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bleeding rate (quantified by the number of packed red blood cells transfused in relation to the duration of ECMO therapy)
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.
Measured: up to 6 months
Secondary outcomes (18)
number of bleeding incidences and severity of bleeding (bleeding grades)
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
Measured: up to six months
Number of Clotting Events
- 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.
Measured: up to six months
Function of the membrane oxygenator
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.
Measured: up to six months
Number of changes of the membrane oxygenator relative to the duration of ECMO therapy
Membrane oxygenators need to be changed due to loss of function (cause by clotting etc.).
Measured: up to six months
Inflammation specific biomarkers (i.e. C-reactive protein, blood counts, reticulated platelets, etc.)
daily routine measurements and frozen plasma
Measured: 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
Global Coagulation assays
Measured: 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
Thromboelastometry
Measured: 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
platelet function analyzer-100
Measured: 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
Fibrinogen levels
Measured: 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
whole blood aggregometry
Measured: 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
D-Dimer levels
Measured: 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
Catecholamines
need for and dose of catecholamines
Measured: 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
cardiac output
Measured: 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
blood pressure
Measured: 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
mortality
by chart review or telephone call
Measured: 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
number of platelet transfusions, fresh frozen plamsa, coagulation interventions etc.
by chart review, number relative to the duration of ECMO therapy
Measured: up to six months
number of platelet transfusions
by chart review, number relative to the duration of ECMO therapy
Measured: up to six months
number of coagulation interventions
by chart review, number relative to the duration of ECMO therapy
Measured: up to six months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2016 (estimated)
- Study startJul 2016
- Primary completionMay 2021
- Study completionJul 2021
Why it stopped: After completion of pilot study (n=50) no effect on primary outcome and limited feasibility of recruitment and study procedures
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Respiratory Distress Syndrome, AdultStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Thomas Staudinger
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Thomas Staudinger, Medical University of Vienna
- Investigators
- Thomas Staudinger, MD, Principal investigator, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02895373
- Sponsor's protocol ID
- ECMO_PGE1_2.1
- Acronym
- ECMO_PGE1
- Status last verified
- Jan 2022
- First submitted
- 30 Jun 2016
- Last updated
- 9 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No: 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)
Publications
Buchtele N, Schorgenhofer C, Schwameis M, Jilma B, Schellongowski P, Herkner H, Riss K, Schmid M, Hermann A, Robak O, Nagler B, Traby L, Bojic A, Staudinger T. Add-On Prostaglandin E1 in Venovenous Extracorporeal Membrane Oxygenation: A Randomized, Double-Blind, Placebo-controlled Pilot Trial. Am J Respir Crit Care Med. 2022 Jul 15;206(2):170-177. doi: 10.1164/rccm.202110-2359OC.
PubMed 35426776
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02895373
- Acronym / sponsor ID
- ECMO_PGE1 / ECMO_PGE1_2.1
- Keywords
- platelet inhibition, alprostadil, extracorporeal membrane oxygenation, bleeding, thromboembolic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: After completion of pilot study (n=50) no effect on primary outcome and limited feasibility of recruitment and study procedures
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Thomas StaudingerUniversity, hospital or other
- Study start
- Jul 2016 (actual)
- Primary completion
- May 2021 (actual)
- Study completion
- Jul 2021 (actual)
- First posted
- 9 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Alprostadil | Experimental | Drug: Alprostadilheparin (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 |
| Placebo | Placebo comparator | Drug: 0.9% sodium chloride solutionheparin (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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- minimum age 18 years
Key exclusion criteria (12 listed)
- • Long- term therapy with other antiplatelet drugs including Acetyl Salicylic Acid
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Alprostadil5ng/kg/min, continuously, start within 24h of initiation of ECMO therapy and end at the end of ECMO therapy | Drug | Alprostadil |
| 0.9% sodium chloride solutioncontinuously, start within 24h of initiation of ECMO therapy and end at the end of ECMO therapy | Drug | Placebo |
Primary outcome
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.
18 secondary outcomes
number of bleeding incidences and severity of bleeding (bleeding grades)
Time frame: up to six months
Number of Clotting Events
Time frame: up to six months
Function of the membrane oxygenator
Time frame: up to six months
Number of changes of the membrane oxygenator relative to the duration of ECMO therapy
Time frame: up to six months
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
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
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
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
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
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
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
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
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
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
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
number of platelet transfusions, fresh frozen plamsa, coagulation interventions etc.
Time frame: up to six months
number of platelet transfusions
Time frame: up to six months
number of coagulation interventions
Time frame: up to six months
Results and safety
The study was stopped early (reason given: After completion of pilot study (n=50) no effect on primary outcome and limited feasibility of recruitment and study procedures). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2022.
- Derived from this study: PubMed 35426776Buchtele N, Schorgenhofer C, Schwameis M, Jilma B, Schellongowski P, Herkner H, Riss K, Schmid M, Hermann A, Robak O, Nagler B, Traby L, Bojic A, Staudinger T. Add-On Prostaglandin E1 in Venovenous Extracorporeal Membrane Oxygenation: A Randomized, Double-Blind, Placebo-controlled Pilot Trial. Am J Respir Crit Care Med. 2022 Jul 15;206(2):170-177. doi: 10.1164/rccm.202110-2359OC.
- Individual participant dataSharing planned: No. 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)
Related trials for Respiratory Distress Syndrome, Adult
Recruiting
REspiratory MEchanics for Delivering Individualised Exogenous Surfactant
Respiratory Distress Syndrome in Premature Infant
Recruiting
WIN Ratio Analysis to Determine a Strategy of Non- Invasive SUpport for Respiratory Failure in the EmeRgency Department
Acute Hypoxic Respiratory Failure, Acute Respiratory Distress Syndrome (ARDS)
RecruitingObservational study
Effect of Transpulmonary MP on Prognosis of Patients With Severe ARDS Treated With VV-ECMO
Acute Respiratory Distress Syndrome, Extracorporeal Membrane Oxygenation
Active, not recruitingObservational study
Longitudinal Recovery Trajectories After an Acute Respiratory Distress Syndrome, a New Understanding
ARDS, ARDS Disease Progression
RecruitingObservational study
Respiratory Distress and Elective Cesarean Section at Term
Respiratory Distress Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas Staudinger, MD principal investigator
Medical University of Vienna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alprostadil and 0.9% sodium chloride solution in people with Respiratory Distress Syndrome, Adult and Extracorporeal Membrane Oxygenation, run by Thomas Staudinger at 1 site in Austria.
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 3 inclusion and 12 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: stopped early, as of the sponsor's last update on 9 Feb 2022. 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 Austria. 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. Some participants in this study may receive a placebo. 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 was stopped early (reason given: After completion of pilot study (n=50) no effect on primary outcome and limited feasibility of recruitment and study procedures). Results are not available in the source record.
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?
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). 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 NCT02895373, which also lists 1 linked publication.
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 9 Feb 2022.