Cardiovascular Surgery, Haemorrhage, Haemostasis
Conditions
Keywords
Surgical treatment of haemorrhage
Brief summary
To demonstrate efficacy and safety of TachoSil® in cardiovascular surgery
Interventions
DRUGfibrinogen (human) + thrombin (human)
DRUGStandard haemostatic treatment in cardiovascular surgery
Any haemostatic fleece material without additional active coagulation stimulating compounds (primarily Surgicel®)
Sponsors
Nycomed
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
All inclusion criteria must be answered yes for a subject to participate in the trial. At Screening: 1. Has the subject given informed consent according to local requirements before any trial related activities? A trial related activity is any procedure that would not have been performed during the routine management of the subject. In this trial the screening is the first trial related activity. 2. For female subjects of childbearing potential: Is the pregnancy test at screening negative? 3. Does the female subject of childbearing potential use adequate contraception (contraceptive pill, contraceptive injection, contraceptive implant or intrauterine device)? 4. Is the subject ≥ 18 years of age? 5. Is the following planned: An elective surgery on the heart, the ascending aorta or arch, requiring cardiopulmonary bypass procedure? Intra operative (after primary haemostatic treatment): 6. Is bleeding from the heart muscle, the pericardium, a major vessel or a vascular bed that requires supportive haemostatic treatment present? 7. Has the area with the most problematic haemorrhage (target area) been identified? (please note that this must be done before randomisation). 8. Is it possible to compress the randomised treatment (TachoSil® or control fleece material) for 3 minutes?
Exclusion criteria
All
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Achieving Haemostasis at 3 Minutes | 3 minutes | Three minutes after application of trial treatment (TachoSil® or standard fleece material) the investigator evaluated if haemostasis in the target area was achieved. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Achieving Haemostasis at 6 Minutes. | 6 minutes | Six minutes after application of trial treatment (TachoSil® or standard fleece material) the investigator evaluated if haemostasis in the target area was achieved. |
Countries
Denmark
Participant flow
Pre-assignment details
From the total of 120 enrolled subjects, data are presented for 119 randomised subjects that received trial treatment (= Intention to Treat (ITT) population).
Participants by arm
| Arm | Count |
|---|---|
| TachoSil® | 59 |
| Standard Treatment | 60 |
| Total | 119 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Other | 2 | 5 |
Baseline characteristics
| Characteristic | TachoSil® | Standard Treatment | Total |
|---|---|---|---|
| Age, Customized 18-65 years | 24 participants | 21 participants | 45 participants |
| Age, Customized 65 years or above | 35 participants | 39 participants | 74 participants |
| Classification of surgery | 44 Percentage of subjects | 59 Percentage of subjects | 103 Percentage of subjects |
| Evaluation of bleeding at target area before randomization Arterial | 48 participants | 40 participants | 88 participants |
| Evaluation of bleeding at target area before randomization Mild haemorrhage | 19 participants | 24 participants | 43 participants |
| Evaluation of bleeding at target area before randomization Moderate haemorrhage | 35 participants | 34 participants | 69 participants |
| Evaluation of bleeding at target area before randomization Severe haemorrhage | 5 participants | 2 participants | 7 participants |
| Evaluation of bleeding at target area before randomization Venous | 11 participants | 20 participants | 31 participants |
| Identification of target area for efficacy evaluation Aorta | 35 participants | 32 participants | 67 participants |
| Identification of target area for efficacy evaluation Coronary anastomosis | 2 participants | 3 participants | 5 participants |
| Identification of target area for efficacy evaluation Internal mammary artery vascular bed | 1 participants | 1 participants | 2 participants |
| Identification of target area for efficacy evaluation Left atrium | 3 participants | 2 participants | 5 participants |
| Identification of target area for efficacy evaluation Left ventricle | 3 participants | 2 participants | 5 participants |
| Identification of target area for efficacy evaluation Other | 3 participants | 2 participants | 5 participants |
| Identification of target area for efficacy evaluation Right atrium | 5 participants | 10 participants | 15 participants |
| Identification of target area for efficacy evaluation Right ventricle | 11 participants | 8 participants | 19 participants |
| Primary haemostatic treatment Clips | 3 participants | 2 participants | 5 participants |
| Primary haemostatic treatment Electro-coagulation | 6 participants | 5 participants | 11 participants |
| Primary haemostatic treatment Gauze | 0 participants | 1 participants | 1 participants |
| Primary haemostatic treatment None | 10 participants | 12 participants | 22 participants |
| Primary haemostatic treatment Suturing | 43 participants | 43 participants | 86 participants |
| Race/Ethnicity, Customized Caucasian | 59 participants | 60 participants | 119 participants |
| Sex: Female, Male Female | 14 Participants | 17 Participants | 31 Participants |
| Sex: Female, Male Male | 45 Participants | 43 Participants | 88 Participants |
| Type of tissue Tissue | 16 participants | 22 participants | 38 participants |
| Type of tissue Vessel | 43 participants | 38 participants | 81 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 38 / 62 | 30 / 57 |
| serious Total, serious adverse events | 8 / 62 | 18 / 57 |
Outcome results
Primary
Proportion of Subjects Achieving Haemostasis at 3 Minutes
Three minutes after application of trial treatment (TachoSil® or standard fleece material) the investigator evaluated if haemostasis in the target area was achieved.
Time frame: 3 minutes
Population: Three subjects were randomised to standard treatment but incorrectly received TachoSil® instead. All other subjects received the trial treatment to which they were randomised. The intention to treat (ITT) population was defined as randomised and the Safety population (= basis for Adverse Events analyses) was defined as treated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TachoSil® | Proportion of Subjects Achieving Haemostasis at 3 Minutes | 0.746 Proportion of Subjects |
| Standard Treatment | Proportion of Subjects Achieving Haemostasis at 3 Minutes | 0.333 Proportion of Subjects |
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Proportion of Subjects Achieving Haemostasis at 6 Minutes.
Six minutes after application of trial treatment (TachoSil® or standard fleece material) the investigator evaluated if haemostasis in the target area was achieved.
Time frame: 6 minutes
Population: Three subjects were randomised to standard treatment but incorrectly received TachoSil® instead. All other subjects received the trial treatment to which they were randomised. The intention to treat (ITT) population was defined as randomised and the Safety population (= basis for Adverse Events analyses) was defined as treated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TachoSil® | Proportion of Subjects Achieving Haemostasis at 6 Minutes. | 0.949 Proportion of Subjects |
| Standard Treatment | Proportion of Subjects Achieving Haemostasis at 6 Minutes. | 0.717 Proportion of Subjects |
p-value: <0.0006Cochran-Mantel-Haenszel