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

Rigshospitalet

Status and phase

Completed

Phase 4

Conditions

Endothelial Dysfunction

Aortic Aneurysm, Thoracic

Treatments

Drug: OctaplasLG®

Biological: Fresh frozen plasma

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT02253082

VIPER-OCTA

H-3-2014-018 (Other Identifier)

Details and patient eligibility

About

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

Full description

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.

Enrollment

44 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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)