Study Of Tranexamic Acid For The Reduction Of Blood Loss In Patients Undergoing Major Abdominal Surgery

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00827931
• Collaborator: (none)
• Enrollment: 94
• Locations: 2
• Arms: 2
• Duration (Months): 19.9
• Patients Per Site: 47
• Patients Per Site Per Month: 2.4

Study Details

Study Description

Brief Summary

Tranexamic acid has been shown to reduce postoperative blood losses and transfusion requirements in various types of major surgery (orthopedic surgery, spine surgery, cardiopulmonary bypass, liver resections, and gynecological cancers).The current trial is being conducted to compare the efficacy of tranexamic acid plus standard of care versus standard of care in reduction of blood loss in patients undergoing major abdominal surgeries.

Condition or Disease	Intervention/Treatment	Phase
Biliary Tract Surgical Procedures; Pancreaticoduodenectomy; Esophagectomy; Colectomy; Gastrectomy	Drug: Tranexamic acid + Standard of Care; Procedure: Standard of Care	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 94 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Prospective Randomized Phase IV Open Label Comparative Study Of Tranexamic Acid Plus Standard Of Care Vs Standard Of Care For The Reduction Of Blood Loss In Patients Undergoing Major Abdominal Surgery
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A end of the operation and on the mornings of the first, second, fourth and seventh postoperative days.	Drug: Tranexamic acid + Standard of Care; Tranexamic acid given slowly intravenously (15 mg/kg body weight) 15 minutes before surgery followed by a second dose at three hour interval from first dose and third dose at three hour interval from the second + standard of care (Standard of care includes the routine surgical and anesthetic techniques being utilized to control blood loss)
Other: B Standard of Care	Procedure: Standard of Care; Standard of care includes the routine surgical and anesthetic techniques being utilized to control blood loss

Outcome Measures

Primary Outcome Measures

1. Post-operative Blood Loss [Post-operation, Day 1, Day 2 up to drain removal]

   Post-operative blood loss was defined as the sum of the drainage volumes measured over post-operative days 1, 2, and at drain removal. It was measured by weighing the drapes/ dressings or swabs prior to soaking to measure difference in weight and checking drain collectors until drains were removed.

Secondary Outcome Measures

1. Intra-operative Blood Loss [Day 1 (End of surgery)]

   Intra-operative blood loss was measured by weighing the drapes/ dressings or swabs prior to soaking to measure difference in weight and checking drain collectors until drains were removed.

2. Total Blood Loss [Baseline through Day 2 post-surgery]

   Total blood loss was defined as the sum of intra-operative and post-operative blood loss. It was measured by weighing the drapes/ dressings or swabs prior to soaking to measure difference in weight and checking drain collectors until drains were removed.

3. Total Blood Loss as Assessed by the Gross' Formula [Baseline through Day 2 post-surgery]

   Gross' formula for estimating total blood loss: Estimated blood volume multiplied by (*) [(hematocrit initial minus hematocrit final) divided by hematocrit average]; where estimated blood volume equals body weight in kilograms (kg) *70 mL/kg.

4. Percentage of Participants Receiving Transfusions [Up to Day 7 post-surgery]

   A uniform transfusion protocol was maintained for all participants in the study. Transfusion to be triggered at 8.0 milligram/deciliter (mg/dL) hemoglobin or hematocrit value of 24 percent.

5. Hemoglobin Levels [End of surgery, Day 1, Day 2, Day 4 and Day 7/End of treatment (EoT) post-surgery]

6. Number of Participants With Deep Vein Thrombosis (DVT) Post Surgery [Day 7 post-surgery]

   DVT was defined if a segment of the deep vein of the lower limb was not compressible or a previous compressive vein became non compressive or there was no flow in the underlying vessel. Symptoms of DVT included pain in the lower limb, localized tenderness, swelling and warmth.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient undergoing major abdominal surgery (Biliary strictures, Pancreatico-duodenectomy, Esophagectomy, Total proctocolectomy, Hemicolectomy, Gastrectomy, Other major abdominal surgeries with similar expected blood loss)

Exclusion Criteria:

• Patients with a platelet count less than 100, 000/mm3 or history of thrombocytopenia.

• Patients with known coagulopathy.

• Patients with anemia (hemoglobin levels less than 8 mg/dl)

• Patients with documented DVT or PE at screening or in past three months.

• Patients with any associated major illness (e.g., severe cardiac or respiratory disease).

• Anticoagulants (other than LMWH or heparin in prophylactic doses to prevent deep vein thrombosis), direct thrombin inhibitors or thrombolytic therapy administered or completed within last week

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Baroda	Gujarat	India	390 001
2	Pfizer Investigational Site	Surat	Gujarat	India	395 001

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00827931
• Other Study ID Numbers: B1461001
• First Posted: Jan 23, 2009
• Last Update Posted: Apr 26, 2012
• Last Verified: Apr 1, 2012

• Keywords provided by Pfizer: tranexamic acid; major abdominal surgery; blood loss
• Additional relevant MeSH terms: Hemorrhage; Tranexamic Acid

Study Results

Participant Flow

Arm/Group Title	Tranexamic Acid Plus Standard of Care	Standard of Care
Arm/Group Description	Tranexamic acid given slowly intravenously (IV) (15 milligram (mg)/kilogram (kg) body weight) 15 minutes before surgery followed by a second dose at 3 hour interval from first dose and third dose at 3 hour interval from the second + Standard of care (included the routine surgical and anesthetic techniques being utilized to control blood loss).	Standard of care included the routine surgical and anesthetic techniques being utilized to control blood loss.
Period Title: Overall Study
STARTED	49	45
COMPLETED	43	39
NOT COMPLETED	6	6

Baseline Characteristics

Arm/Group Title	Tranexamic Acid Plus Standard of Care	Standard of Care	Total
Arm/Group Description	Tranexamic acid given slowly intravenously (IV) (15 milligram (mg)/kilogram (kg) body weight) 15 minutes before surgery followed by a second dose at 3 hour interval from first dose and third dose at 3 hour interval from the second + Standard of care (included the routine surgical and anesthetic techniques being utilized to control blood loss).	Standard of care included the routine surgical and anesthetic techniques being utilized to control blood loss.	Total of all reporting groups
Overall Participants	49	45	94
Age, Customized (Number) [Number]
18 to 44 years	24 49%	16 35.6%	40 42.6%
45 to 64 years	21 42.9%	22 48.9%	43 45.7%
Greater than or equal to 65 years	4 8.2%	7 15.6%	11 11.7%
Sex: Female, Male (Count of Participants)
Female	16 32.7%	16 35.6%	32 34%
Male	33 67.3%	29 64.4%	62 66%

Outcome Measures

1. Primary Outcome

Title	Post-operative Blood Loss
Description	Post-operative blood loss was defined as the sum of the drainage volumes measured over post-operative days 1, 2, and at drain removal. It was measured by weighing the drapes/ dressings or swabs prior to soaking to measure difference in weight and checking drain collectors until drains were removed.
Time Frame	Post-operation, Day 1, Day 2 up to drain removal

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) population included all randomized participants in compliance with the intent-to-treat analysis principle. Participants who had no post-baseline data for a given endpoint was not included in the analysis of that endpoint.

Arm/Group Title	Tranexamic Acid Plus Standard of Care	Standard of Care
Arm/Group Description	Tranexamic acid given slowly intravenously (IV) (15 milligram (mg)/kilogram (kg) body weight) 15 minutes before surgery followed by a second dose at 3 hour interval from first dose and third dose at 3 hour interval from the second + Standard of care (included the routine surgical and anesthetic techniques being utilized to control blood loss).	Standard of care included the routine surgical and anesthetic techniques being utilized to control blood loss.
Measure Participants	23	21
Mean (Standard Deviation) [milliliter (mL)]	394.3 (366.36)	494.3 (503.94)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tranexamic Acid Plus Standard of Care, Standard of Care
	Comments	The null hypothesis applicable to the efficacy analyses was that there was no difference between tranexamic acid plus standard care compared to standard care alone. The alternative hypothesis was that there was a difference.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.460
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-99.9
	Confidence Interval	(2-Sided) 95%; -371.4 to 171.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 131.99
	Estimation Comments

2. Secondary Outcome

Title	Intra-operative Blood Loss
Description	Intra-operative blood loss was measured by weighing the drapes/ dressings or swabs prior to soaking to measure difference in weight and checking drain collectors until drains were removed.
Time Frame	Day 1 (End of surgery)

Outcome Measure Data

Analysis Population Description

FAS population included all randomized participants in compliance with the intent-to-treat analysis principle. Participants who had no post-baseline data for a given endpoint was not included in the analysis of that endpoint.

Arm/Group Title	Tranexamic Acid Plus Standard of Care	Standard of Care
Arm/Group Description	Tranexamic acid given slowly intravenously (IV) (15 milligram (mg)/kilogram (kg) body weight) 15 minutes before surgery followed by a second dose at 3 hour interval from first dose and third dose at 3 hour interval from the second + Standard of care (included the routine surgical and anesthetic techniques being utilized to control blood loss).	Standard of care included the routine surgical and anesthetic techniques being utilized to control blood loss.
Measure Participants	23	21
Mean (Standard Deviation) [mL]	599.2 (419.58)	682.8 (555.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tranexamic Acid Plus Standard of Care, Standard of Care
	Comments	The null hypothesis applicable to the efficacy analyses was that there was no difference between tranexamic acid plus standard care compared to standard care alone. The alternative hypothesis was that there was a difference.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.579
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-83.6
	Confidence Interval	(2-Sided) 95%; -386.5 to 219.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 147.61
	Estimation Comments

3. Secondary Outcome

Title	Total Blood Loss
Description	Total blood loss was defined as the sum of intra-operative and post-operative blood loss. It was measured by weighing the drapes/ dressings or swabs prior to soaking to measure difference in weight and checking drain collectors until drains were removed.
Time Frame	Baseline through Day 2 post-surgery

Outcome Measure Data

Analysis Population Description

FAS population included all randomized participants in compliance with the intent-to-treat analysis principle. Participants who had no post-baseline data for a given endpoint was not included in the analysis of that endpoint.

Arm/Group Title	Tranexamic Acid Plus Standard of Care	Standard of Care
Arm/Group Description	Tranexamic acid given slowly intravenously (IV) (15 milligram (mg)/kilogram (kg) body weight) 15 minutes before surgery followed by a second dose at 3 hour interval from first dose and third dose at 3 hour interval from the second + Standard of care (included the routine surgical and anesthetic techniques being utilized to control blood loss).	Standard of care included the routine surgical and anesthetic techniques being utilized to control blood loss.
Measure Participants	23	21
Mean (Standard Deviation) [mL]	993.6 (703.63)	1177.1 (879.94)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tranexamic Acid Plus Standard of Care, Standard of Care
	Comments	The null hypothesis applicable to the efficacy analyses was that there was no difference between tranexamic acid plus standard care compared to standard care alone. The alternative hypothesis was that there was a difference.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.452
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-183.5
	Confidence Interval	(2-Sided) 95%; -672.6 to 305.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 239.19
	Estimation Comments

4. Secondary Outcome

Title	Total Blood Loss as Assessed by the Gross' Formula
Description	Gross' formula for estimating total blood loss: Estimated blood volume multiplied by (*) [(hematocrit initial minus hematocrit final) divided by hematocrit average]; where estimated blood volume equals body weight in kilograms (kg) *70 mL/kg.
Time Frame	Baseline through Day 2 post-surgery

Outcome Measure Data

Analysis Population Description

FAS population included all randomized participants in compliance with the intent-to-treat analysis principle. Participants who had no post-baseline data for a given endpoint was not included in the analysis of that endpoint.

Arm/Group Title	Tranexamic Acid Plus Standard of Care	Standard of Care
Arm/Group Description	Tranexamic acid given slowly intravenously (IV) (15 milligram (mg)/kilogram (kg) body weight) 15 minutes before surgery followed by a second dose at 3 hour interval from first dose and third dose at 3 hour interval from the second + Standard of care (included the routine surgical and anesthetic techniques being utilized to control blood loss).	Standard of care included the routine surgical and anesthetic techniques being utilized to control blood loss.
Measure Participants	23	21
Mean (Standard Deviation) [mL]	17.8 (451.24)	435.5 (558.74)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tranexamic Acid Plus Standard of Care, Standard of Care
	Comments	The null hypothesis applicable to the efficacy analyses was that there was no difference between tranexamic acid plus standard care compared to standard care alone. The alternative hypothesis was that there was a difference.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-417.7
	Confidence Interval	(2-Sided) 95%; -729.4 to -106.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 152.51
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants Receiving Transfusions
Description	A uniform transfusion protocol was maintained for all participants in the study. Transfusion to be triggered at 8.0 milligram/deciliter (mg/dL) hemoglobin or hematocrit value of 24 percent.
Time Frame	Up to Day 7 post-surgery

Outcome Measure Data

Analysis Population Description

FAS population included all randomized participants in compliance with the intent-to-treat analysis principle. Participants who had no post-baseline data for a given endpoint was not included in the analysis of that endpoint.

Arm/Group Title	Tranexamic Acid Plus Standard of Care	Standard of Care
Arm/Group Description	Tranexamic acid given slowly intravenously (IV) (15 milligram (mg)/kilogram (kg) body weight) 15 minutes before surgery followed by a second dose at 3 hour interval from first dose and third dose at 3 hour interval from the second + Standard of care (included the routine surgical and anesthetic techniques being utilized to control blood loss).	Standard of care included the routine surgical and anesthetic techniques being utilized to control blood loss.
Measure Participants	23	21
Number (95% Confidence Interval) [Percentage of participants]	21.7 44.3%	14.3 31.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tranexamic Acid Plus Standard of Care, Standard of Care
	Comments	Fisher's exact test was used at 5% level of significance.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.701
	Comments
	Method	Fisher Exact
	Comments

6. Secondary Outcome

Title	Hemoglobin Levels
Time Frame	End of surgery, Day 1, Day 2, Day 4 and Day 7/End of treatment (EoT) post-surgery

Outcome Measure Data

Analysis Population Description

FAS population included all randomized participants in compliance with the intent-to-treat analysis principle. Participants who had no post-baseline data for a given endpoint was not included in the analysis of that endpoint.

Arm/Group Title	Tranexamic Acid Plus Standard of Care	Standard of Care
Arm/Group Description	Tranexamic acid given slowly intravenously (IV) (15 milligram (mg)/kilogram (kg) body weight) 15 minutes before surgery followed by a second dose at 3 hour interval from first dose and third dose at 3 hour interval from the second + Standard of care (included the routine surgical and anesthetic techniques being utilized to control blood loss).	Standard of care included the routine surgical and anesthetic techniques being utilized to control blood loss.
Measure Participants	23	21
End of surgery	11.6 (2.16)	12.1 (1.30)
Day 1	11.3 (1.44)	11.6 (1.41)
Day 2	10.4 (1.70)	11.0 (1.41)
Day 4	10.8 (1.67)	10.9 (1.39)
Day 7/EoT	11.0 (1.38)	11.1 (1.60)

7. Secondary Outcome

Title	Number of Participants With Deep Vein Thrombosis (DVT) Post Surgery
Description	DVT was defined if a segment of the deep vein of the lower limb was not compressible or a previous compressive vein became non compressive or there was no flow in the underlying vessel. Symptoms of DVT included pain in the lower limb, localized tenderness, swelling and warmth.
Time Frame	Day 7 post-surgery

Outcome Measure Data

Analysis Population Description

FAS population included all randomized participants in compliance with the intent-to-treat analysis principle. Participants who had no post-baseline data for a given endpoint was not included in the analysis of that endpoint.

Arm/Group Title	Tranexamic Acid Plus Standard of Care	Standard of Care
Arm/Group Description	Tranexamic acid given slowly intravenously (IV) (15 milligram (mg)/kilogram (kg) body weight) 15 minutes before surgery followed by a second dose at 3 hour interval from first dose and third dose at 3 hour interval from the second + Standard of care (included the routine surgical and anesthetic techniques being utilized to control blood loss).	Standard of care included the routine surgical and anesthetic techniques being utilized to control blood loss.
Measure Participants	23	21
Number [Participants]	0 0%	0 0%

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Tranexamic Acid Plus Standard of Care		Standard of Care
Arm/Group Description	Tranexamic acid given slowly intravenously (IV) (15 milligram (mg)/kilogram (kg) body weight) 15 minutes before surgery followed by a second dose at 3 hour interval from first dose and third dose at 3 hour interval from the second + Standard of care (included the routine surgical and anesthetic techniques being utilized to control blood loss).		Standard of care included the routine surgical and anesthetic techniques being utilized to control blood loss.
All Cause Mortality
	Tranexamic Acid Plus Standard of Care		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Tranexamic Acid Plus Standard of Care		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/49 (18.4%)		7/45 (15.6%)
Cardiac disorders
Bradycardia	0/49 (0%)		1/45 (2.2%)
Cardio-respiratory arrest	2/49 (4.1%)		3/45 (6.7%)
Myocardial infarction	0/49 (0%)		1/45 (2.2%)
Gastrointestinal disorders
Intestinal obstruction	0/49 (0%)		1/45 (2.2%)
Vomiting	1/49 (2%)		0/45 (0%)
General disorders
Asthenia	1/49 (2%)		0/45 (0%)
Hepatobiliary disorders
Biliary tract disorder	1/49 (2%)		1/45 (2.2%)
Infections and infestations
Infectious peritonitis	1/49 (2%)		1/45 (2.2%)
Sepsis	1/49 (2%)		0/45 (0%)
Septic shock	1/49 (2%)		0/45 (0%)
Injury, poisoning and procedural complications
Biliary anastomosis complication	0/49 (0%)		1/45 (2.2%)
Post procedural complication	1/49 (2%)		0/45 (0%)
Suture rupture	2/49 (4.1%)		0/45 (0%)
Metabolism and nutrition disorders
Hypokalaemia	1/49 (2%)		0/45 (0%)
Nervous system disorders
Convulsion	0/49 (0%)		1/45 (2.2%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	0/49 (0%)		2/45 (4.4%)
Aspiration	0/49 (0%)		1/45 (2.2%)
Pneumonitis	1/49 (2%)		0/45 (0%)
Respiratory distress	1/49 (2%)		0/45 (0%)
Other (Not Including Serious) Adverse Events
	Tranexamic Acid Plus Standard of Care		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/49 (44.9%)		14/45 (31.1%)
Blood and lymphatic system disorders
Anaemia	5/49 (10.2%)		1/45 (2.2%)
Thrombocytopenia	1/49 (2%)		0/45 (0%)
Gastrointestinal disorders
Ascites	2/49 (4.1%)		0/45 (0%)
Diarrhoea	1/49 (2%)		0/45 (0%)
Nausea	0/49 (0%)		1/45 (2.2%)
Vomiting	1/49 (2%)		1/45 (2.2%)
General disorders
Pain	1/49 (2%)		0/45 (0%)
Pyrexia	2/49 (4.1%)		1/45 (2.2%)
Infections and infestations
Abscess	0/49 (0%)		1/45 (2.2%)
Post procedural infection	1/49 (2%)		0/45 (0%)
Injury, poisoning and procedural complications
Cardiac procedure complication	1/49 (2%)		0/45 (0%)
Procedural hypertension	1/49 (2%)		0/45 (0%)
Procedural pain	4/49 (8.2%)		4/45 (8.9%)
Investigations
Blood glucose increased	0/49 (0%)		1/45 (2.2%)
Blood pressure decreased	1/49 (2%)		2/45 (4.4%)
Haematocrit decreased	1/49 (2%)		3/45 (6.7%)
Haemoglobin decreased	1/49 (2%)		3/45 (6.7%)
Metabolism and nutrition disorders
Hypokalaemia	2/49 (4.1%)		0/45 (0%)
Nervous system disorders
Bradykinesia	0/49 (0%)		1/45 (2.2%)
Headache	0/49 (0%)		1/45 (2.2%)
Psychiatric disorders
Delirium	0/49 (0%)		1/45 (2.2%)
Sleep disorder	1/49 (2%)		0/45 (0%)
Skin and subcutaneous tissue disorders
Urticaria	0/49 (0%)		1/45 (2.2%)
Urticaria contact	0/49 (0%)		1/45 (2.2%)
Vascular disorders
Deep vein thrombosis	1/49 (2%)		0/45 (0%)
Hypertension	2/49 (4.1%)		0/45 (0%)
Hypotension	4/49 (8.2%)		1/45 (2.2%)

Limitations/Caveats

The intended FAS population was planned to include participants from 2 sites, however due to non-reliability of data from one of the sites, the actual FAS population included participants from a single site only.

More Information

Certain Agreements

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

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.