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BleedingPhase 2ZEPLAST-PEDNCT04434001

ZEPLAST- PED: ZEro_PLASma Trial in Small Infants Undergoing Cardiac Surgery

A Phase 2 study testing Fibrinogen Concentrate Human, Prothrombin Complex Concentrate and Fresh Frozen Plasma in people with Bleeding and Cardiac Defect, run by IRCCS Policlinico S. Donato at 1 site in Italy.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

In pediatric patients (newborns and infants weighing less than 10 kg) undergoing cardiac surgery with extracorporeal circulation postoperative bleeding represents a known complication with a significant impact on outcome. Read more about this study

Who is it for?
Ages 1 day to 2 years
Conditions the study is for
Bleeding, Cardiac Defect, Surgery--Complications
What is being tested?
Fibrinogen Concentrate Human, Prothrombin Complex Concentrate and Fresh Frozen Plasma
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteItaly
Study dates
27 Feb 2020to 30 Jun 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 1 day to 2 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • newborns and infants with weight lower than 10 kg undergoing cardiac surgery with extracorporeal circulation:
  • informed consent signed by both parents or legal guardian.

Who cannot join

  • emergency surgery;
  • known congenital coagulopathy or suspected based on anamnesis;
  • participation to other clinical trials;
  • known hypersensitivity to components and excipients of FFP , prothrombin complex concentrate or fibrinogen concentrate.

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • IRCCS Policlinico San Donato

    San Donato Milanese, MI, 20097

Other trials in Italy

About this study

Official title: ZEPLAST- PED: ZEro_PLASma Trial in Small Infants Undergoing Cardiac Surgery Randomized Controlled Pilot Phase II Study

In pediatric patients (newborns and infants weighing less than 10 kg) undergoing cardiac surgery with extracorporeal circulation postoperative bleeding represents a known complication with a significant impact on outcome. Fresh frozen plasma (FFP) for bleeding management is associated, particularly in this kind of patients, to volume overload and a significative increase of Transfusion Related Acute Lung Injury (TRALI), further worsening the postoperative outcome. In the adult patient FFP employment could be almost completely canceled by administration of concentrated hemostatic components - the fibrinogen concentrate and prothrombin complex concentrate (PCC). We designed this phase II pilot study to establish whether an analogous strategy, modified accordingly to pediatric physiology, could be safely and successfully applied in newborns and infants.

Read the detailed description

The study population will be randomized to two groups: ZEPLAST and control, respectively.

The two groups will receive the same priming solution (containing Red Blood Cells and albumin 5%) and heparin/protamine management. In both groups coagulation will be assessed with rotational thromboelastometry (ROTEM - EXTEM, INTEM, HEPTEM and FIBTEM tests) after heparin antagonization. In case of bleeding, coagulopathies will be treated differently:

  • in the ZEPLAST group, fibrinogen deficiency (FIBTEM Maximum Clot Firmness MCF < 8 mm) will be treated with 30 mg/kg of concentrated fibrinogen; low thrombin generation (EXTEM Clotting Time CT > 100 s) will be treated with 20 mg/kg of prothrombin complex concentrate;
  • in the control group, coagulopathies will be treated with 10-20 ml/kg of FFP. In case of refractory bleeding, PCC and fibrinogen can be administered as a rescue treatment.

Further ROTEM tests will be performed at 24 and 48 hours post surgery. Outcome parameters will be collected at the same timepoints.

Being tested
Fibrinogen Concentrate Human, Prothrombin Complex Concentrate, Fresh Frozen Plasma
Keywords
bleeding, pediatric cardiac surgery, fresh frozen plasma, fibrinogen concentrate, prothrombin complex concentrate
Medical subject headings
Hemorrhage, Afibrinogenemia, Transfusion-Related Acute Lung Injury, Transfusion Reaction, Heart Defects, Congenital, Hemophilia B

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Fibrinogen Concentrate HumanDrug

    Also called Haemocomplettan

    Treatment of acquired postoperatively fibrinogen deficiency as assessed by ROTEM FIBTEM test.

  • Prothrombin Complex ConcentrateDrug

    Also called Confidex

    Treatment of acquired postoperatively thrombin generation deficiency as assessed by ROTEM EXTEM test.

  • Fresh Frozen PlasmaBiological

    Treatment of acquired postoperative coagulopathy as assessed by ROTEM FIBTEM and INTEM tests.

Study groups in NCT04434001
Study groupRoleWhat they receive
ZEPLASTExperimentalIn case of bleeding and: * CT INTEM > CT HEPTEM by 25% : give protamine 0.25 mg/kg; * MCF FIBTEM < 8 mm : give Fibrinogen Concentrate 30 mg/kg; * CT EXTEM > 100 s : give Prothrombin Complex Concentrate 20 mg/kg.
Receives: Drug: Fibrinogen Concentrate Human; Drug: Prothrombin Complex Concentrate
ControlActive comparatorIn case of bleeding and: * CT INTEM > CT HEPTEM by 25% : give protamine 0.25 mg/kg; * fibrinogen and/or thrombin generation deficiency : give FFP 10-20 ml/kg.
Receives: Biological: Fresh Frozen Plasma

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Transfusion of Fresh Frozen Plasma (FFP)

    Number of patients transfused with FFP

    Measured: First 48 hours after surgery

Secondary outcomes (3)

  1. Postoperative bleeding

    Amount of blood collected by chest drainages

    Measured: First 12, 24 and 48 hours after surgery

  2. Severe bleeding

    Number of patients who experienced severe bleeding (higher than 30 ml/kg in the first 12 hours after surgery)

    Measured: First 12 hours after surgery

  3. Surgical re-exploration for bleeding

    Number of patients requiring surgical re-exploration due to bleeding (bleeding with no coagulopathies detected or refractory to pharmacological treatment)

    Measured: First 12, 24 and 48 hours after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jun 2020
  2. Study start27 Feb 2020
  3. Primary completion31 May 2021
  4. Study completion30 Jun 2021

Why it stopped: The study encountered unexpected difficulties in enrolling patients due to requirements for the Informed Consent. 60% of our patients comes from abroad with only one accompanying parent. The rules of our EC require both parents to sign the consent.

Resources

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
Single blind
Who is masked
Participant
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04434001
Sponsor's protocol ID
ZEPLAST-PED
Acronym
ZEPLAST-PED
Status last verified
Oct 2021
First submitted
12 Jun 2020
Last updated
3 Nov 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Moore SB. Transfusion-related acute lung injury (TRALI): clinical presentation, treatment, and prognosis. Crit Care Med. 2006 May;34(5 Suppl):S114-7. doi: 10.1097/01.CCM.0000214312.20718.3E.

    PubMed 16617254

  • Ranucci M, Baryshnikova E. Fibrinogen supplementation after cardiac surgery: insights from the Zero-Plasma trial (ZEPLAST). Br J Anaesth. 2016 May;116(5):618-23. doi: 10.1093/bja/aev539. Epub 2016 Feb 17.

    PubMed 26893405

  • Bianchi P, Cotza M, Beccaris C, Silvetti S, Isgro G, Pome G, Giamberti A, Ranucci M; Surgical and Clinical Outcome REsearch (SCORE) group. Early or late fresh frozen plasma administration in newborns and small infants undergoing cardiac surgery: the APPEAR randomized trial. Br J Anaesth. 2017 May 1;118(5):788-796. doi: 10.1093/bja/aex069.

    PubMed 28510741

  • Ranucci M, Bianchi P, Cotza M, Beccaris C, Silvetti S, Isgro G, Giamberti A, Baryshnikova E. Fibrinogen levels and postoperative chest drain blood loss in low-weight (<10 kg) children undergoing cardiac surgery. Perfusion. 2019 Nov;34(8):629-636. doi: 10.1177/0267659119854246. Epub 2019 Jun 28.

    PubMed 31250738

  • Hayes K, Fernando MC, Jordan V. Prothrombin complex concentrate in cardiac surgery for the treatment of coagulopathic bleeding. Cochrane Database Syst Rev. 2022 Nov 21;11(11):CD013551. doi: 10.1002/14651858.CD013551.pub2.

    PubMed 36408876

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fibrinogen Concentrate Human, Prothrombin Complex Concentrate and Fresh Frozen Plasma in people with Bleeding and Cardiac Defect, run by IRCCS Policlinico S. Donato 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 2 inclusion and 4 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 3 Nov 2021. 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 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: The study encountered unexpected difficulties in enrolling patients due to requirements for the Informed Consent. 60% of our patients comes from abroad with only one accompanying parent. The rules of our EC require both parents to sign the consent.). 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?

Transfusion of Fresh Frozen Plasma (FFP) (time frame: First 48 hours after surgery). 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 NCT04434001, which also lists 5 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 3 Nov 2021.

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