Vasculopathic Injury and Plasma as Endothelial Rescue - OCTAplas Trial (EudraCT no. 2014-000452-28)

NCT ID: NCT02253082

Last Updated: 2016-12-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

44 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-11-30

Study Completion Date

2016-12-31

Brief Summary

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Effects of OctaplasLG® on endothelial integrity in patients undergoing emergency surgery for thoracic aortic dissections - a randomized, controlled, single-blinded investigator-initiated pilot trial

Detailed Description

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Trial Name: VIPER-OCTA trial - Vasculopathic Injury and Plasma as Endothelial Rescue - OCTAplas trial

Background

* Patients operated for thoracic aortic dissections in deep hypothermic circulatory arrest are prone to develop postoperative renal failure secondary to severe endothelial dysfunction and capillary leakage, and currently no therapy addressing this complication has proven successful
* Data from animal models of shock and massively bleeding patients indicate that plasma may be beneficial for re-establishing endothelial integrity
* Patients operated for thoracic aortic dissections generally develop requirement for massive transfusion during surgery
* Current guidelines, however, recommend against plasma transfusion to patients not needing coagulation factor replacement due to the inherent risk of transfusion complications
* OctaplasLG® is an immune complex-free and cell-free, pathogen inactivated standardized plasma product that has been shown not to be related to the transfusion complications seen secondary to standard fresh frozen plasma (FFP), thus, OctaplasLG® may be a beneficial, alternative resuscitation fluid in patients with severe endothelial dysfunction/damage
* The purpose is to bridge the knowledge gap regarding the effect of OctaplasLG® on endothelial integrity and safety

Design Single-centre randomised, single-blinded, controlled, investigator-initiated pilot trial of 42 patients undergoing emergency surgery for thoracic aortic dissections randomized to administration of OctaplasLG®, as compared to standard FFP, as coagulation factor replacement related to bleeding, when need for coagulation factor replacement is deemed necessary by the clinician according to local protocol.

Inclusion criteria

* Patient eligible for emergency surgery on cardiopulmonary bypass pump for a thoracic aortic dissections AND
* Age \> 18 years AND
* Consent obtainable from patient or by proxy (independent physicians and/or next of kin)

Exclusion criteria

* Documented refusal of blood transfusion OR
* FFP transfusion before randomization OR
* Aortic dissection due to trauma OR
* Treatment with GPIIb/IIIa inhibitors \< 24h from screening OR
* Withdrawal from active therapy OR
* Expected to die \< 24h OR
* Previously within 30 days included in a randomized trial, if known at the time of enrolment.
* Known immunoglobulin A (IgA) deficiency with documented antibodies against IgA
* Known hypersensitivity to OctaplasLG®: the active substance, any of the excipients (Sodium citrate dihydrate, Sodium dihydrogenphosphate dihydrate or Glycine) or residues from the manufacturing process (Tri (N-Butyl) Phosphate (TNBP) and Octoxynol (Triton X-100))
* Known severe deficiencies of protein S
* Pregnancy (non-pregnancy confirmed by patient being postmenopausal or having a negative serum-hCG).

Randomization Blood Bank staff will perform 24 hour on-site randomisation by envelope-opening to allow for immediate allocation to either receiving OctaplasLG® (intervention) or standard FFP (control) as coagulation factor replacement.

Outcome measures

Primary outcome measure:

• Plasma levels of endothelial markers (Syndecan-1, soluble thrombomodulin (sTM), sE-selectin, sVE-cadherin) at 24 hours after arrival in ICU for postoperative care, as compared to baseline

Secondary outcome measures:

* Plasma levels of endothelial markers (Syndecan-1, sTM, sE-selectin, sVE-cadherin) at 48 hours postoperatively, as compared to baseline
* Acute Kidney Injury (AKI) according to RIFLE Criteria in the first 7 postoperative days, see appendix 1
* Renal replacement therapy
* Sepsis-Related Organ Failure Assessment (SOFA), worst score during ICU stay, see appendix 2
* 30-day and 90-day mortality
* P-CRP, IL-6, P-Catecholamines at 24 hours and 48 hours
* Length of stay in ICU and hospital
* Severe adverse reactions

Tertiary outcome measures

* TRALI
* TACO

Trial size The calculation is based in part by data collected in a quality control investigation of the effect of OctaplasLG® vs. FFP. The power calculation is based on the finding of a significantly higher relative level of sTM in the FFP compared to the OctaplasLG® group (p=0.025). The relative values of sTM post-CPB: FFP group: mean 3.35 (SD 2.12); OctaplasLG® group: mean 1.70 (SD 0.49); SD across the entire group of patients: 1.574. To detect the above difference with a power of 0.90 (1-β) and alpha of 0.05 requires n=21 patients in each group. The investigators have chosen to include 42 patients, 21 evaluable patients in each randomization group in case of attrition, in the present trial.

Conditions

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Aortic Aneurysm, Thoracic Endothelial Dysfunction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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OctaplasLG®

replacement to bleeding

Group Type ACTIVE_COMPARATOR

OctaplasLG®

Intervention Type DRUG

OctaplasLG® is an industrial donor plasma product pooled from approximately 400 single donor units. It possess' unique features when compared to standard FFP, such as having standardized concentrations of natural pro- and anti-coagulation factors, standardized volume and as being pathogen free. Very importantly, the manufacturing method of OctaplasLG® removes immune complexes and cells in several steps of microfiltration in addition to viral, bacterial and prion pathogen inactivation.

Standard fresh frozen plasma

replacement to bleeding

Group Type PLACEBO_COMPARATOR

Fresh frozen plasma

Intervention Type BIOLOGICAL

Standard FFP from the Blood Bank

Interventions

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OctaplasLG®

OctaplasLG® is an industrial donor plasma product pooled from approximately 400 single donor units. It possess' unique features when compared to standard FFP, such as having standardized concentrations of natural pro- and anti-coagulation factors, standardized volume and as being pathogen free. Very importantly, the manufacturing method of OctaplasLG® removes immune complexes and cells in several steps of microfiltration in addition to viral, bacterial and prion pathogen inactivation.

Intervention Type DRUG

Fresh frozen plasma

Standard FFP from the Blood Bank

Intervention Type BIOLOGICAL

Other Intervention Names

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Octaplas FFP

Eligibility Criteria

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Inclusion Criteria

* Patient eligible for emergency surgery on cardiopulmonary bypass pump for a thoracic aortic dissections AND
* Age \> 18 years AND
* Consent obtainable from patient or by proxy (independent physicians and/or next of kin)

Exclusion Criteria

* Documented refusal of blood transfusion OR
* FFP transfusion before randomization OR
* Aortic dissection due to trauma OR
* Treatment with GPIIb/IIIa inhibitors \< 24h from screening OR
* Withdrawal from active therapy OR
* Expected to die \< 24h OR
* Previously within 30 days included in a randomized trial, if known at the time of enrolment
* Known IgA deficiency with documented antibodies against IgA
* Known hypersensitivity to OctaplasLG®: the active substance, any of the excipients (Sodium citrate dihydrate, Sodium dihydrogenphosphate dihydrate or Glycine) or residues from the manufacturing process (Tri (N-Butyl) Phosphate (TNBP) and Octoxynol (Triton X-100))
* Known severe deficiencies of protein S
* Pregnancy (non-pregnancy confirmed by patient being postmenopausal or having a negative serum-hCG)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Octapharma

INDUSTRY

Sponsor Role collaborator

Rigshospitalet, Denmark

OTHER

Sponsor Role lead

Responsible Party

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Jakob Stensballe, MD, PhD

MD, PhD, Consultant

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jakob Stensballe, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Rigshospitalet, Denmark

Locations

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Rigshospitalet, Copenhagen University Hospital

Copenhagen, , Denmark

Site Status

Countries

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Denmark

References

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Stensballe J, Ulrich AG, Nilsson JC, Henriksen HH, Olsen PS, Ostrowski SR, Johansson PI. Resuscitation of Endotheliopathy and Bleeding in Thoracic Aortic Dissections: The VIPER-OCTA Randomized Clinical Pilot Trial. Anesth Analg. 2018 Oct;127(4):920-927. doi: 10.1213/ANE.0000000000003545.

Reference Type DERIVED
PMID: 29863610 (View on PubMed)

Other Identifiers

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H-3-2014-018

Identifier Type: OTHER

Identifier Source: secondary_id

VIPER-OCTA

Identifier Type: -

Identifier Source: org_study_id