Endothelial Dysfunction Clinical Trial
Official title:
Effects of OctaplasLG® on Endothelial Integrity in Patients Undergoing Emergency Surgery for Thoracic Aortic Dissections - a Randomized, Controlled, Single-blinded Investigator-initiated Pilot Trial
Effects of OctaplasLG® on endothelial integrity in patients undergoing emergency surgery for thoracic aortic dissections - a randomized, controlled, single-blinded investigator-initiated pilot trial
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.
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment
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