Clinical Trials Logo

Clinical Trial Summary

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


Clinical Trial 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. ;


Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment


Related Conditions & MeSH terms


NCT number NCT02253082
Study type Interventional
Source Rigshospitalet, Denmark
Contact
Status Completed
Phase Phase 4
Start date November 2014
Completion date December 2016

See also
  Status Clinical Trial Phase
Completed NCT02122198 - Vascular Mechanisms for the Effects of Loss of Ovarian Hormone Function on Cognition in Women N/A
Completed NCT04156711 - Remote Ischemic Preconditioning in Patients Undergoing Acute Minor Abdominal Surgery N/A
Recruiting NCT06133634 - Fisetin to Improve Vascular Function in Older Adults Phase 1/Phase 2
Completed NCT05872139 - Role of Mitochondrial-derived Oxidative Stress to Promote Vascular Endothelial Dysfunction in Non-exercisers With Aging N/A
Recruiting NCT04558450 - Covid-19 Effects on Arterial Stiffness and Vascular Aging (CARTESIAN) N/A
Terminated NCT03325933 - Resistance Training and Cardiometabolic Health N/A
Not yet recruiting NCT05939934 - Impact of the Mandibular Advancement Device on Sleep Apnea During CPAP Withdrawal N/A
Completed NCT02652975 - Anticancer Treatment of Breast Cancer Related to Cardiotoxicity and Dysfunctional Endothelium N/A
Recruiting NCT02334839 - The Association Between Severity of Hypertensive Disorder During Pregnancy and Endothelial Dysfunction N/A
Recruiting NCT02020044 - Outcome After Descemet Membrane Endothelial Keratoplasty (DMEK) and Ultra-thin Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) N/A
Completed NCT01691404 - Study on the Effects of Epicatechin and Quercetin Supplementation on Vascular Function and Blood Pressure (FLAVO) N/A
Completed NCT01775865 - Targeting Inflammation to Treat Cardiovascular Aging Phase 2
Terminated NCT01412216 - The Effects of Sedentarism on Vascular Function, Inflammation, and Insulin Resistance Phase 2
Completed NCT01319344 - Effect of Eplerenone on Endothelial Function in Metabolic Syndrome Phase 3
Completed NCT00990730 - Atherosclerosis in Rheumatoid Arthritis N/A
Completed NCT00848302 - Endothelial Function in Human Arteries Early Phase 1
Completed NCT00987974 - Short Term Statin Treatment and Endothelial Dysfunction Due to Ischemia and Reperfusion Injury Phase 4
Completed NCT00532844 - A Phase 2, Pharmacokinetic (PK) Study of 6R-BH4 Alone or 6R-BH4 With Vitamin C in Subjects With Endothelial Dysfunction Phase 2
Completed NCT00376246 - Effect of Ezetimibe on Flow-mediated Brachial Artery Reactivity in Healthy Subjects Phase 4
Completed NCT00775099 - Combustion Derived Air Pollution and Vascular Function N/A