Prophylactic Suture Line Sealing With NE'X Glue R-eco in Cardiac and Vascular Surgery

A Prospective ClinicaL investigatiOn Evaluating Prophylactic Sealing of sUture Lines Using the NE'X Glue R-eco Surgical AdhesivE in Cardiac and (Cardio)Vascular Anastomotic Repair Procedures

This clinical study aims to evaluate the effectiveness and safety of using NE'X Glue R-eco to seal suture lines. The adhesive will be applied to reduce the risk of suture line bleeding in cardiac or vascular repair surgeries, a prosthetic or biologic graft, patch, or allograft.

The effectiveness of the adhesive will be assessed after restoring blood flow.

Suture line bleeding is a common issue in cardiovascular surgeries, leading to serious complications and increased costs. Effective management is crucial to prevent morbidity, fatal consequences, and the need for reoperation, which has high mortality rates. Blood transfusions carry risks, and patients who avoid them tend to recover better. Advances in surgical techniques and the use of anticoagulants have increased the need for robust methods to prevent suture line bleeding.

Surgical adhesives are becoming standard practice to prevent air and liquid leaks during surgeries. Different classes of adhesives, such as cyanoacrylates, polyethylene glycol polymers, bovine serum albumin (BSA) and glutaraldehyde mixtures, gelatin and thrombin sealants, and fibrin sealants, offer various advantages and disadvantages.

Most cyanoacrylate sealants are used externally due to risks of infection, cytotoxicity, and tissue necrosis when used internally. They are effective for closing skin incisions, trauma wounds, and providing a microbial barrier over closed wounds. Polyethylene glycol hydrogel adhesives are valued for their biocompatibility, degradability, and tunable mechanical properties, acting as both fluid barriers and hemostatic agents. However, they can cause significant post-polymerization swelling. Fibrin sealants, derived from blood, are used as hemostatic agents in cardiac, liver, and splenic surgeries. They carry risks of transmitting infections and air or gas embolism. Gelatin and thrombin mixtures are versatile hemostatic agents used in various surgeries, including delicate structures like nerves, due to their low toxicity.

The last class of surgical adhesives includes mixtures of bovine serum albumin (BSA) and glutaraldehyde (GA) or polyaldehyde. In BioGlue® (CryoLife Inc.) and PREVELEAKTM (Baxter Advanced Surgery), BSA crosslinks with extracellular proteins to form a mechanical seal independent of the coagulation system. NE'X Glue R-eco, a new adhesive by Grena BioMed Limited, is similar to BioGlue® but uses recombinant human serum albumin (rHSA) instead of BSA. Both adhesives use a double-chambered syringe for controlled application.

BioGlue® has proven biocompatibility, reliability, and safety, with minor differences in external shape compared to NE'X Glue R-eco. BioGlue® has passed extensive biological evaluations and animal studies, demonstrating its effectiveness in surgical repairs.

Analytical and functional tests have shown that NE'X Glue R-eco has adequate bonding strength and similar chemical properties to BioGlue®. The safety and benefits of these adhesives have been demonstrated in various studies. This pivotal study aims to evaluate the efficacy and safety of NE'X Glue R-eco for sealing suture lines. The study will assess immediate and delayed suture line sealing, sealing time, use of additional agents, product handling, blood loss, use of blood replacement products, anticoagulant/antiplatelet medication intake, device deficiencies, and peri- and postoperative complications and re-interventions.

The primary objective of this study is to evaluate the immediate sealing of suture lines using NE'X Glue R-eco. The secondary objective is to assess the overall efficacy and safety of NE'X Glue R-eco for prophylactic suture line sealing.

This clinical investigation uses a single-arm, non-randomized design to evaluate the safety and effectiveness of surgical adhesives in cardiac and vascular procedures. Strict inclusion and exclusion criteria prevent bias, ensuring participants represent the general population needing these surgeries. Exclusion criteria include hypersensitivity, active infection, vasculitis, bleeding disorders, immune suppression, and refusal of blood transfusions. Clinical Research Associates will monitor the study and report any deviations.

Participants will be followed for up to 3 months post-surgery to document potential complications such as inflammatory responses, allergic reactions, tissue necrosis, vessel obstruction, thrombosis, and more. This follow-up period allows for clear documentation of safety and effectiveness.

Patients undergoing large vessel and cardiac repair, arterial reconstruction, or arteriovenous graft formation with prosthetic or biologic grafts (patches) or allografts will be included in this study. Data will be collected from 60 patients at sites in Belgium and Poland. Inclusion and exclusion criteria ensure a diverse participant cohort reflective of the broader population. Minors, pregnant women, and breastfeeding women are excluded. Female participants of childbearing age must use contraception and undergo pregnancy testing. Incapacitated patients may be included if their medical condition prevents informed consent. Follow-up monitoring will be conducted for up to 3 months post-procedure.

Inclusion Criteria:

• Patient ≥ 18 years of age at study entry.
• Patient is scheduled for open procedures for surgical placement of a prosthetic or biologic graft (patch) or an allograft for cardiac and (cardio)vascular anastomosis repair. Emergency, transplantation and minimally invasive procedures are excluded. Patients receiving long-term anticoagulation, including antiplatelet agent, are included. Choice of graft is at the discretion of the surgeon.
• Patient is willing and able to be contacted for up to 3 months (± 14 days) follow-up.
• Patient or legal representative and investigator signed and dated the informed consent form prior to the index-procedure.

Exclusion Criteria:

• Patient has a known hypersensitivity, contraindication, or allergic reaction to albumin or glutaraldehyde.
• Patient has a history of bleeding diathesis or coagulopathy.
• Presence of active infection or contamination in the to be grafted area or the vicinity.
• Known vasculitis in the to be grafted area.
• Patient takes immune suppressive medication like prednisone resulting in weakening of the vessel wall.
• Patient is refusing blood transfusion.
• Patient or legal representative is unable / unwilling to provide informed consent.
• Patient is unable to comply with the protocol or proposed follow-up visits.
• Female patient is pregnant, lactating, or planning pregnancy during the clinical investigation.
• Female participants of childbearing age must agree to use safe contraception (e.g., intrauterine devices, hormonal contraceptives: contraceptive pills, implants, transdermal patches hormonal vaginal devices, injections with prolonged release, abstinence).
• Patients who are currently enrolled in another clinical study, or have recently participated in a clinical study, that could potentially interfere with the outcomes or introduce bias into the results of the current study (as determined by the investigator). This includes studies involving investigational drugs, medical devices, or other interventions that could impact the safety, efficacy, or scientific integrity of this study.