VeraSeal

VeraSeal should only be used by an experienced surgeon who has been trained in its use. It is available as two prefilled syringes in a syringe holder, one containing a solution of human fibrinogen, and the other containing a solution of human thrombin. Before use, the syringes are attached to a device supplied with the medicine that allows their contents to mix as they are dripped or sprayed on the wound. The amount of VeraSeal to be used depends on a number of factors, including the type of surgery, the size of the wound and the number of applications.

The active substances in VeraSeal, fibrinogen and thrombin, are proteins present in human plasma (the liquid part of the blood), which are involved in the blood clotting process.

When the two active substances are mixed, thrombin cuts fibrinogen up into fibrin (protein involved in forming blood clots in the body). The fibrin then aggregates (sticks together) and forms a fibrin clot that helps the wound to heal, preventing bleeding.

Three main studies in 614 patients, mainly adults, found that VeraSeal is effective at stopping bleeding within 4 minutes of applying it during surgery.

In one study of blood vessel surgery, VeraSeal worked better than manual compression, with 76% of patients having no bleeding 4 minutes after treatment with VeraSeal (83 out of 109), compared with 23% after manual compression (13 out of 57).

In a second study of organ surgery, VeraSeal was as effective as another product Surgicel: 93% of the patients had no bleeding 4 minutes after treatment with VeraSeal (103 out of 111), while 81% of the patients had no bleeding with Surgicel (91 out of 113).

In a third study of soft tissue surgery, VeraSeal was as effective as Surgicel: 83% of the patients had no bleeding 4 minutes after treatment with VeraSeal (96 out of 116), compared with 78% of the patients after treatment with Surgicel (84 out of 108).

A fourth study was carried out in 178 children and adolescents who received either VeraSeal or another medicine containing fibrinogen and thrombin (Evicel) to stop bleeding during surgery. In this study, 97% (88 out of 91) of patients given VeraSeal had no bleeding 4 minutes after treatment and no new bleeding requiring treatment until the end of the surgery, compared with 95% (83 out of 87) of patients given Evicel.

For the full list of side effects and restrictions with VeraSeal, see the package leaflet.

The most common side effects with VeraSeal (which may affect up to 1 in 10 people) include nausea (feeling sick), pruritus (itchiness) and procedural pain (pain from the surgery). Rarely, VeraSeal may cause an allergic reaction which can be severe especially when the medicine is used repeatedly. In rare cases, patients may develop antibodies to the proteins in VeraSeal, which could interfere with blood clotting. Thromboembolic complications (blood clots) may occur if VeraSeal is accidentally injected into a blood vessel.

VeraSeal must not be used intravascularly (inside blood vessels) or to treat heavy bleeding of the arteries.

VeraSeal has been shown to effectively stop bleeding during surgery, which can be expected to reduce blood loss, reduce time in the operating theatre and possibly shorten hospital stays. Although patients could develop antibodies against the medicine, which might reduce its effectiveness, this has not been seen in the studies.

The observed side effects were as expected with major surgeries or the patient’s condition. The European Medicines Agency therefore decided that VeraSeal’s benefits are greater than its risks and it can be authorised for use in the EU.

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of VeraSeal have been included in the summary of product characteristics and the package leaflet.

As for all medicines, data on the use of VeraSeal are continuously monitored. Side effects reported with VeraSeal are carefully evaluated and any necessary action taken to protect patients.

VeraSeal received a marketing authorisation valid throughout the EU on 10 November 2017.

VeraSeal is a medicine that contains the active substances human fibrinogen and human thrombin. It was to be available as two separate solutions that are mixed together to prepare a sealant that is applied to the surface of blood vessels.

VeraSeal was expected to be used to help stop bleeding during vascular surgery when standard surgical methods for controlling bleeding are insufficient.

The active substances in VeraSeal, human fibrinogen and human thrombin, are natural proteins in the blood and are obtained from blood donors. When applied to a moist surface, the thrombin is activated and cuts fibrinogen up into smaller units called fibrin. The fibrin then aggregates (sticks together) and forms fibrin clots on the surface of blood vessels. This helps prevent bleeding and seals the blood vessels.

The applicant presented data from one main study involving 167 patients who underwent vascular surgery. In this study, bleeding during surgery was managed either by applying VeraSeal or by applying manual pressure (a standard way of stopping bleeding during surgery). The main measure of effectiveness was the ability to stop bleeding during a 10-minute observation period, after applying the method to stop the bleeding.

The application was withdrawn after the CHMP had evaluated the documentation provided by the company and formulated lists of questions. After the CHMP had assessed the company's responses to the last round of questions, there were still some unresolved issues.

Based on the review of the data and the company's response to the CHMP lists of questions, at the time of the withdrawal the CHMP had concerns and was of the provisional opinion that VeraSeal could not have been approved to help stop bleeding during vascular surgery.

The Committee was concerned that the main study had not been carried out in accordance with the guidelines for Good Clinical Practice (GCP). Findings from a GCP inspection of the study sites raised serious questions about the data from the main study submitted in support of the application. Therefore, at the time of the withdrawal, the CHMP was of the opinion that the company had not provided enough data to support the application for VeraSeal.

In its letter notifying the Agency of the withdrawal of the applications, the company stated that the withdrawal was due to not being able to gather the additional data required by the CHMP, including data from three ongoing clinical studies with the product, within the available timeframe.

The company informed the CHMP that there are currently no ongoing compassionate use programmes for VeraSeal. There are no consequences for patients in the three ongoing clinical trials. If you are in a clinical trial and need more information about your treatment, contact the doctor who is giving it to you.