Extracorporeal Membrane OxygenationPhase 2/3NCT03208270
Antithrombin Supplementation in ECMO
A Phase 2/3 study testing Antithrombin supplementation and No antithrombin supplementation in people with Extracorporeal Membrane Oxygenation, run by Policlinico Hospital at 1 site in Italy.
Trial summary
Bleeding is the most feared complication during extracorporeal membrane oxygenation (ECMO) and is associated with high dosing of heparin. There is no consensus on antithrombin (AT) supplementation during ECMO. However, AT is needed by heparin to properly anticoagulate. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Extracorporeal Membrane Oxygenation
- What is being tested?
- Antithrombin supplementation and No antithrombin supplementation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteItaly
- Study dates
- 28 Jul 2017to 15 May 2019
- Phase
- Phase 2/3
- 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
- patients requiring veno-venous ECMO for severe respiratory failure.
Who cannot join
- patients with pre-existent heparin-induced thrombocytopenia
Trial locations and contacts
1 site in 1 country.
Italy1 site
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, MI, 20122
About this study
Official title: Pilot Study of Antithrombin Supplementation During Extracorporeal Membrane Oxigenation
Bleeding is the most feared complication during extracorporeal membrane oxygenation (ECMO) and is associated with high dosing of heparin. There is no consensus on antithrombin (AT) supplementation during ECMO. However, AT is needed by heparin to properly anticoagulate. We hypothesize that maintaining normal antithrombin levels during ECMO is associated with a less heparin dosing and more adequate level of anticoagulation.
Read the detailed description
Extracorporeal membrane oxygenation (ECMO) is a life support for patients with severe acute respiratory failure when conventional treatments failed but it is accompanied by a significant risk of bleeding. Heparin is required during ECMO to avoid circuit thrombosis and its anticoagulant effect is strictly dependent on antithrombin (AT). AT also plays a central role in mediating inflammation. Acquired AT deficiency is common in patients on ECMO, arguably due to long term anticoagulation in addition to sepsis itself. Guidelines suggest to supplement AT in ECMO only when its deficiency coexists with heparin resistance. Few studies evaluated the effect of AT supplementation during ECMO without a consensus on the appropriate level to be maintained. AT supplementation increase anti-Factor Xa (anti-Xa) levels without increasing heparin dosage. This may have a clinical impact because risk of bleeding during ECMO is associated with higher heparin dosage.
We hypothesize that maintaining normal antithrombin activity levels (80%-120%) during ECMO is associated with: I. less heparin dosage, II. a more adequate level of anticoagulation, III. less hemostasis related complications, and IV. a lower level of inflammation.
Adult patients on veno-venous ECMO for respiratory failure will be randomized to maintain AT between 80% and 100% (study group) or no supplementation unless heparin resistance occurs (control group). Sample size of at least 20 patients per group (n=40) is calculated upon the primary outcome measure of reduction of heparin use in the study group compared to the control group. AT and anti-Xa will be measured before ECMO and daily while on ECMO. Anticoagulation will be guaranteed with unfractionated heparin infusion with a target aPTT 1.5-2X normal. Study will end at ECMO removal.
Consistent literature suggests that current ECMO anticoagulation strategies are suboptimal probably due to improper antithrombin supplementation. A normal antithrombin level could guarantee an adequate anticoagulation regimen.
- Conditions
- Extracorporeal Membrane Oxygenation
- Being tested
- Antithrombin supplementation, No antithrombin supplementation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Antithrombin supplementationDrug
Also called Antithtrombin
antithrombin concentrate will be supplemented to maintain a functional antithrombin level between 80%-120%
No antithrombin supplementationDrug
Also called No antithrombin
supplementation of antithrombin will not be provided unless "heparin resistance" occurs
| Study group | Role | What they receive |
|---|---|---|
| Antithrombin supplementation | Experimental | Patients randomized to the study group will receive supplementation of antithrombin concentrate to maintain a functional antithrombin level between 80%-120%. Receives: Drug: Antithrombin supplementation |
| No Antithrombin supplementation | Active comparator | Patients randomized to the control group will never receive supplementation of antithrombin unless "heparin resistance" occurs. Receives: Drug: No antithrombin supplementation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Amount of heparin
Heparin dosage to maintain aPTT ratio between 1.5-2
Measured: through study completion, an average of 10 days
Secondary outcomes (4)
Bleeding
Bleeding complications
Measured: through study completion, an average of 10 days
Adequacy of anticoagulation
Adequacy of anticoagulation, assessed through Anti-Xa levels
Measured: through study completion, an average of 10 days
thrombosis
Patient's or circuit thrombosis
Measured: through study completion, an average of 10 days
transfusions
Blood products transfusion requirements
Measured: through study completion, an average of 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2017
- Study start28 Jul 2017
- Primary completion15 May 2019
- Study completion15 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Extracorporeal Membrane OxygenationStudies 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 2/3
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Policlinico Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
- Responsible party
- Principal investigator, Mauro Panigada, MD, Policlinico Hospital
- Investigators
- Mauro Panigada, MD, Principal investigator, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03208270
- Sponsor's protocol ID
- GATRA2016
- Other IDs
- 2016-004534-23, 2016
- Status last verified
- May 2019
- First submitted
- 1 Jul 2017
- Last updated
- 17 May 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Panigada M, Spinelli E, De Falco S, Consonni D, Novembrino C, Boscolo Anzoletti M, Panarello G, Occhipinti G, Dos Santos CC, Pesenti A, Arcadipane A, Grasselli G. The relationship between antithrombin administration and inflammation during veno-venous ECMO. Sci Rep. 2022 Aug 22;12(1):14284. doi: 10.1038/s41598-022-17227-7.
PubMed 35995816Panigada M, Spinelli E, Cucino A, Cipriani E, De Falco S, Panarello G, Occhipinti G, Arcadipane A, Sales G, Fanelli V, Brazzi L, Novembrino C, Consonni D, Pesenti A, Grasselli G. Antithrombin supplementation during extracorporeal membrane oxygenation: study protocol for a pilot randomized clinical trial. Trials. 2019 Jun 11;20(1):349. doi: 10.1186/s13063-019-3386-4.
PubMed 31186035
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Antithrombin Supplementation During Extracorporeal Membrane Oxigenation
- ClinicalTrials.gov ID
- NCT03208270
- Acronym / sponsor ID
- GATRA2016
- Conditions
- Extracorporeal Membrane Oxygenation
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Policlinico HospitalUniversity, hospital or other
- Collaborators
- The Mediterranean Institute for Transplantation and Advanced Specialized Therapies
- Study start
- 28 Jul 2017 (actual)
- Primary completion
- 15 May 2019 (actual)
- Study completion
- 15 May 2019 (actual)
- First posted
- 5 Jul 2017 (actual)
- 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 is the most feared complication during extracorporeal membrane oxygenation (ECMO) and is associated with high dosing of heparin. There is no consensus on antithrombin (AT) supplementation during ECMO. However, AT is needed by heparin to properly anticoagulate. We hypothesize that maintaining normal antithrombin levels during ECMO is associated with a less heparin dosing and more adequate level of anticoagulation.
Detailed description
Extracorporeal membrane oxygenation (ECMO) is a life support for patients with severe acute respiratory failure when conventional treatments failed but it is accompanied by a significant risk of bleeding. Heparin is required during ECMO to avoid circuit thrombosis and its anticoagulant effect is strictly dependent on antithrombin (AT). AT also plays a central role in mediating inflammation. Acquired AT deficiency is common in patients on ECMO, arguably due to long term anticoagulation in addition to sepsis itself. Guidelines suggest to supplement AT in ECMO only when its deficiency coexists with heparin resistance. Few studies evaluated the effect of AT supplementation during ECMO without a consensus on the appropriate level to be maintained. AT supplementation increase anti-Factor Xa (anti-Xa) levels without increasing heparin dosage. This may have a clinical impact because risk of bleeding during ECMO is associated with higher heparin dosage.
We hypothesize that maintaining normal antithrombin activity levels (80%-120%) during ECMO is associated with: I. less heparin dosage, II. a more adequate level of anticoagulation, III. less hemostasis related complications, and IV. a lower level of inflammation.
Adult patients on veno-venous ECMO for respiratory failure will be randomized to maintain AT between 80% and 100% (study group) or no supplementation unless heparin resistance occurs (control group). Sample size of at least 20 patients per group (n=40) is calculated upon the primary outcome measure of reduction of heparin use in the study group compared to the control group. AT and anti-Xa will be measured before ECMO and daily while on ECMO. Anticoagulation will be guaranteed with unfractionated heparin infusion with a target aPTT 1.5-2X normal. Study will end at ECMO removal.
Consistent literature suggests that current ECMO anticoagulation strategies are suboptimal probably due to improper antithrombin supplementation. A normal antithrombin level could guarantee an adequate anticoagulation regimen.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Antithrombin supplementation | Experimental | Drug: Antithrombin supplementationPatients randomized to the study group will receive supplementation of antithrombin concentrate to maintain a functional antithrombin level between 80%-120%. |
| No Antithrombin supplementation | Active comparator | Drug: No antithrombin supplementationPatients randomized to the control group will never receive supplementation of antithrombin unless "heparin resistance" occurs. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- patients requiring veno-venous ECMO for severe respiratory failure.
Key exclusion criteria (1 listed)
- patients with pre-existent heparin-induced thrombocytopenia
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 |
|---|---|---|
| Antithrombin supplementationAlso: Antithtrombinantithrombin concentrate will be supplemented to maintain a functional antithrombin level between 80%-120% | Drug | Antithrombin supplementation |
| No antithrombin supplementationAlso: No antithrombinsupplementation of antithrombin will not be provided unless "heparin resistance" occurs | Drug | No Antithrombin supplementation |
Primary outcome
Amount of heparin
Time frame: through study completion, an average of 10 days
Heparin dosage to maintain aPTT ratio between 1.5-2
4 secondary outcomes
Bleeding
Time frame: through study completion, an average of 10 days
Adequacy of anticoagulation
Time frame: through study completion, an average of 10 days
thrombosis
Time frame: through study completion, an average of 10 days
transfusions
Time frame: through study completion, an average of 10 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2019.
- Derived from this study: PubMed 35995816Panigada M, Spinelli E, De Falco S, Consonni D, Novembrino C, Boscolo Anzoletti M, Panarello G, Occhipinti G, Dos Santos CC, Pesenti A, Arcadipane A, Grasselli G. The relationship between antithrombin administration and inflammation during veno-venous ECMO. Sci Rep. 2022 Aug 22;12(1):14284. doi: 10.1038/s41598-022-17227-7.
- Derived from this study: PubMed 31186035Panigada M, Spinelli E, Cucino A, Cipriani E, De Falco S, Panarello G, Occhipinti G, Arcadipane A, Sales G, Fanelli V, Brazzi L, Novembrino C, Consonni D, Pesenti A, Grasselli G. Antithrombin supplementation during extracorporeal membrane oxygenation: study protocol for a pilot randomized clinical trial. Trials. 2019 Jun 11;20(1):349. doi: 10.1186/s13063-019-3386-4.
- Individual participant dataSharing planned: No
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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.
Mauro Panigada, MD principal investigator
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Antithrombin supplementation and No antithrombin supplementation in people with Extracorporeal Membrane Oxygenation, run by Policlinico Hospital at 1 site in Italy.
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 1 inclusion and 1 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: finished, as of the sponsor's last update on 17 May 2019. 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 Italy. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Amount of heparin (time frame: through study completion, an average of 10 days). 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 NCT03208270, which also lists 2 linked publications.
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 17 May 2019.