TachoSil® Versus Standard Haemostatic Treatment of Haemorrhage in Cardiovascular Surgery (TC-023-IM)

• Sponsor: Nycomed (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00440401
• Collaborator: (none)
• Enrollment: 120
• Location: 1
• Arms: 2
• Duration (Months): 9
• Patients Per Site Per Month: 13.4

Study Details

Study Description

Brief Summary

To demonstrate efficacy and safety of TachoSil® in cardiovascular surgery

Condition or Disease	Intervention/Treatment	Phase
Haemorrhage; Haemostasis; Cardiovascular Surgery	Drug: fibrinogen (human) + thrombin (human); Drug: Standard haemostatic treatment in cardiovascular surgery	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomised, Open Label, Parallel-group, Multi-centre Trial to Compare the Efficacy and Safety of TachoSil® Versus Standard Haemostatic Treatment in Cardiovascular Surgery
• Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: Aug 1, 2007
• Actual Study Completion Date: Nov 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: TachoSil®	Drug: fibrinogen (human) + thrombin (human)
Active Comparator: Standard Treatment Standard Treatment of haemorrhage in cardiovascular surgery	Drug: Standard haemostatic treatment in cardiovascular surgery; Any haemostatic fleece material without additional active coagulation stimulating compounds (primarily Surgicel®)

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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):

1. Is bleeding from the heart muscle, the pericardium, a major vessel or a vascular bed that requires supportive haemostatic treatment present?

2. Has the area with the most problematic haemorrhage (target area) been identified? (please note that this must be done before randomisation).

3. Is it possible to compress the randomised treatment (TachoSil® or control fleece material) for 3 minutes?

Exclusion Criteria:

All exclusion criteria must be answered "no" for a subject to participate in the trial.

At Screening:

1. Has the subject participated in any other trial with an investigational drug or device within 30 days before inclusion in this trial?

2. Does the subject participate in a clinical trial concomitantly with the present trial?

3. Is the subject undergoing an emergency operation?

4. Has the subject a history of allergic reactions after application of human fibrinogen, human thrombin and/or collagen of any origin?

5. Is the subject suffering from known coagulopathy?

6. Is the subject currently participating or has the subject previously participated in the TC-023-IM trial?

7. Is the female subject pregnant or breast feeding?

Intra operative (after primary haemostatic treatment):

1. Has liquid fibrin sealant/glue or TachoSil® been applied?

2. Has the following occurred: Disseminated intravascular coagulation (DIC), i.e. micro vascular bleeding?

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nycomed	Roskilde		Denmark	4000

Sponsors and Collaborators

• Nycomed

Investigators

• Study Chair: Nycomed Clinical Trial Operations, Headquaters

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00440401
• Other Study ID Numbers: TC-023-IM
• First Posted: Feb 27, 2007
• Last Update Posted: May 8, 2012
• Last Verified: Jul 1, 2010

• Keywords provided by , ,: Surgical treatment of haemorrhage
• Additional relevant MeSH terms: Hemorrhage; Thrombin; Hemostatics

Study Results

Participant Flow

Pre-assignment Detail	From the total of 120 enrolled subjects, data are presented for 119 randomised subjects that received trial treatment (= Intention to Treat (ITT) population).

Arm/Group Title	TachoSil®	Comparator
Arm/Group Description	Absorbable sponge for intra-operative topical application	Standard haemostatic treatment in cardiovascular surgery
Period Title: Overall Study
STARTED	59	60
COMPLETED	55	54
NOT COMPLETED	4	6

Baseline Characteristics

Arm/Group Title	TachoSil®	Standard Treatment	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	59	60	119
Age, Customized (participants) [Number]
18-65 years	24 40.7%	21 35%	45 37.8%
65 years or above	35 59.3%	39 65%	74 62.2%
Sex: Female, Male (Count of Participants)
Female	14 23.7%	17 28.3%	31 26.1%
Male	45 76.3%	43 71.7%	88 73.9%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	59 100%	60 100%	119 100%
Classification of surgery (Percentage of subjects) [Number]
Number [Percentage of subjects]	44	59	103
Evaluation of bleeding at target area before randomization (participants) [Number]
Arterial	48 81.4%	40 66.7%	88 73.9%
Venous	11 18.6%	20 33.3%	31 26.1%
Mild haemorrhage	19 32.2%	24 40%	43 36.1%
Moderate haemorrhage	35 59.3%	34 56.7%	69 58%
Severe haemorrhage	5 8.5%	2 3.3%	7 5.9%
Identification of target area for efficacy evaluation (participants) [Number]
Aorta	35 59.3%	32 53.3%	67 56.3%
Coronary anastomosis	2 3.4%	3 5%	5 4.2%
Internal mammary artery vascular bed	1 1.7%	1 1.7%	2 1.7%
Left atrium	3 5.1%	2 3.3%	5 4.2%
Left ventricle	3 5.1%	2 3.3%	5 4.2%
Right atrium	5 8.5%	10 16.7%	15 12.6%
Right ventricle	11 18.6%	8 13.3%	19 16%
Other	3 5.1%	2 3.3%	5 4.2%
Primary haemostatic treatment (participants) [Number]
Suturing	43 72.9%	43 71.7%	86 72.3%
Electro-coagulation	6 10.2%	5 8.3%	11 9.2%
Clips	3 5.1%	2 3.3%	5 4.2%
Gauze	0 0%	1 1.7%	1 0.8%
None	10 16.9%	12 20%	22 18.5%
Type of tissue (participants) [Number]
Tissue	16 27.1%	22 36.7%	38 31.9%
Vessel	43 72.9%	38 63.3%	81 68.1%

Outcome Measures

1. Primary Outcome

Title	Proportion of Subjects Achieving Haemostasis at 3 Minutes
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	TachoSil®	Standard Treatment
Arm/Group Description
Measure Participants	59	60
Number (95% Confidence Interval) [Proportion of Subjects]	0.746	0.333

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TachoSil®, Standard Treatment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Normal approximation to the binominal distribution is used to construct the asymptotic confidence intervals

2. Secondary Outcome

Title	Proportion of Subjects Achieving Haemostasis at 6 Minutes.
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	TachoSil®	Standard Treatment
Arm/Group Description
Measure Participants	59	60
Number (95% Confidence Interval) [Proportion of Subjects]	0.949	0.717

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TachoSil®, Standard Treatment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0006
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Normal approximation to the binominal distribution is used to construct the asymptotic confidence intervals

Adverse Events

Adverse Event Reporting Description	SAE/AE assessment by neutral questioning "Have you experienced any health problems since the last contact?" by the investigator at each contact (visit or phone). Basis for analysis was the safety population (= all subjects randomised and given trial treatment).
Arm/Group Title	TachoSil®		Standard Treatment
Arm/Group Description
All Cause Mortality
	TachoSil®		Standard Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	TachoSil®		Standard Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/62 (12.9%)		18/57 (31.6%)
Cardiac disorders
Atrial fibrillation	1/62 (1.6%)	1	4/57 (7%)	4
Atrioventricular block third degree	0/62 (0%)	0	4/57 (7%)	4
Cardiac arrest	0/62 (0%)	0	1/57 (1.8%)	1
Cardiac tamponade	1/62 (1.6%)	2	1/57 (1.8%)	1
Low cardiac output syndrome	0/62 (0%)	0	2/57 (3.5%)	2
Myocardial infarction	0/62 (0%)	0	2/57 (3.5%)	2
Ventricular tachycardia	0/62 (0%)	0	2/57 (3.5%)	2
Gastrointestinal disorders
Colitis ischaemic	0/62 (0%)	0	1/57 (1.8%)	1
General disorders
Multi-organ failure	2/62 (3.2%)	2	1/57 (1.8%)	1
Infections and infestations
Mediastinitis	1/62 (1.6%)	1	0/57 (0%)	0
Pneumonia klebsiella	0/62 (0%)	0	1/57 (1.8%)	1
Postoperative wound infection	0/62 (0%)	0	1/57 (1.8%)	1
Sepsis	0/62 (0%)	0	2/57 (3.5%)	2
Staphylococcal bacteraemia	1/62 (1.6%)	1	0/57 (0%)	0
Wound infection	2/62 (3.2%)	2	0/57 (0%)	0
Wound infection staphylococcal	1/62 (1.6%)	1	0/57 (0%)	0
Injury, poisoning and procedural complications
Brain contusion	0/62 (0%)	0	1/57 (1.8%)	1
Cardiac function disturbance postoperative	1/62 (1.6%)	1	0/57 (0%)	0
Haemothorax	0/62 (0%)	0	1/57 (1.8%)	1
Post procedural haemorrhage	1/62 (1.6%)	1	0/57 (0%)	0
Post procedural stroke	0/62 (0%)	0	1/57 (1.8%)	1
Stent-graft endoleak	0/62 (0%)	0	1/57 (1.8%)	1
Nervous system disorders
Cerebral infarction	1/62 (1.6%)	1	0/57 (0%)	0
Cerebrovascular accident	0/62 (0%)	0	1/57 (1.8%)	1
Vocal cord paralysis	0/62 (0%)	0	1/57 (1.8%)	1
Psychiatric disorders
Mental disorder due to a general medical condition	0/62 (0%)	0	1/57 (1.8%)	1
Renal and urinary disorders
Renal failure acute	1/62 (1.6%)	1	1/57 (1.8%)	1
Tubulointerstitial nephritis	1/62 (1.6%)	1	1/57 (1.8%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/62 (0%)	0	1/57 (1.8%)	1
Pleural effusion	0/62 (0%)	0	2/57 (3.5%)	5
Pneumothorax	0/62 (0%)	0	2/57 (3.5%)	2
Pulmonary embolism	0/62 (0%)	0	1/57 (1.8%)	1
Respiratory failure	0/62 (0%)	0	1/57 (1.8%)	1
Vascular disorders
Haemorrhage	0/62 (0%)	0	1/57 (1.8%)	1
Hypotension	0/62 (0%)	0	1/57 (1.8%)	1
Other (Not Including Serious) Adverse Events
	TachoSil®		Standard Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/62 (61.3%)		30/57 (52.6%)
Blood and lymphatic system disorders
Haemorrhagic anaemia	5/62 (8.1%)	5	6/57 (10.5%)	6
Cardiac disorders
Atrial fibrillation	17/62 (27.4%)	17	10/57 (17.5%)	10
Bradycardia	1/62 (1.6%)	1	3/57 (5.3%)	3
Pericardial effusion	3/62 (4.8%)	3	4/57 (7%)	4
Tachyarrhythmia	4/62 (6.5%)	4	4/57 (7%)	4
Gastrointestinal disorders
Constipation	3/62 (4.8%)	3	3/57 (5.3%)	3
Nausea	8/62 (12.9%)	8	5/57 (8.8%)	5
General disorders
Pyrexia	4/62 (6.5%)	4	3/57 (5.3%)	3
Injury, poisoning and procedural complications
Post procedural haemorrhage	2/62 (3.2%)	2	3/57 (5.3%)	3
Investigations
Haemoglobin decreased	0/62 (0%)	0	3/57 (5.3%)	3
Metabolism and nutrition disorders
Hyperglycaemia	6/62 (9.7%)	6	7/57 (12.3%)	7
Psychiatric disorders
Psychotic disorder	0/62 (0%)	0	4/57 (7%)	4
Respiratory, thoracic and mediastinal disorders
Pleural effusion	14/62 (22.6%)	14	9/57 (15.8%)	9
Pneumothorax	4/62 (6.5%)	4	2/57 (3.5%)	3
Vascular disorders
Hypotension	2/62 (3.2%)	2	4/57 (7%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.