Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery

NCT03376061 | Completed Phase 4 Results DMC

• 1 other identifier: DEPOSITION 1.0 2017-07-28
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 1

Brief Summary

The aim is to conduct a double-blinded single-centre randomized controlled clinical trial of application of topical dose of tranexamic acid (TA) versus the usual intravenous TA in patients undergoing cardiac surgery at the Hamilton General Hospital. This pilot study will assess the feasibility to perform a large randomized international trial exploring this objective.

Conditions

Bleeding; Surgical Blood Loss

Keywords

Tranexamic Acid; Cardiac surgery

Outcome Measures

Primary Outcomes (1)

• Median Volume of Mediastinal Fluid Collected From Participants

  Cumulative volume (mL) of fluid collected from mediastinal drainage tubes 24 hours after the surgical procedure

  Fluid collected in the first 24 hours after the surgical procedure

Secondary Outcomes (6)

• Number of Participants With Seizures

  Patients will be followed post-operatively until hospital discharge

• Number of Participants With Mortality

  Patients will be followed post-operatively until hospital discharge

• Number of Participants With RBC Transfusion

  Intra-operative and post-operative RBC transfusions

• Number of Participants With Re-operation for Bleeding or Tamponade

  Patients will be followed post-operatively until hospital discharge

• Median Number of Hours Participants Spent in ICU

  Number of hours spent in ICU from arrival to exit (collected at the Post-Operative Visit).

Study Arms (2)

TA Topical

ACTIVE COMPARATOR

1 syringe of 50ml of topical Tranexamic Acid (5g) or placebo. The topical will be poured into the pericardial mediastinal cavities in 2 equal doses, 25ml when the pt comes off-pump and the other 25ml before sternotomy is closed.

Drug: Tranexamic Acid

TA Intravenous

ACTIVE COMPARATOR

2 syringes of 50ml (5mg) Tranexamic Acid for intravenous injection or placebo.

Drug: Tranexamic Acid

Interventions

Tranexamic Acid DRUG

Tranexamic Acid is a medication used to treat or prevent excessive blood loss from major trauma, post partum, surgery, tooth removal, nose bleeds, and heavy menstruation.

Also known as: Cyklokapron

TA Intravenous; TA Topical

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female \>= 18 years old
• Undergoing cardiac surgical procedure with the use of cardiopulmonary bypass and median sternotomy
• Provide written informed consent

You may not qualify if:

• Poor (English) language comprehension
• Minimally invasive valve surgery
• Off-pump procedures
• Emergency operations
• Known history of increased bleeding disorder
• Thromboembolic disease
• Allergy to tranexamic acid
• Severe renal impairment (eGFR \<30 mL/min/1.73m2 )

Sponsors & Collaborators

• Population Health Research Institute: lead

Study Sites (1)

Hamilton General Hospital

Hamilton, Ontario, L8L 2X2, Canada

Location

Related Publications (9)

• Kucuk O, Kwaan HC, Frederickson J, Wade L, Green D. Increased fibrinolytic activity in patients undergoing cardiopulmonary bypass operation. Am J Hematol. 1986 Nov;23(3):223-9. doi: 10.1002/ajh.2830230306.

  PMID: 3766524 BACKGROUND

• Harker LA, Malpass TW, Branson HE, Hessel EA 2nd, Slichter SJ. Mechanism of abnormal bleeding in patients undergoing cardiopulmonary bypass: acquired transient platelet dysfunction associated with selective alpha-granule release. Blood. 1980 Nov;56(5):824-34. No abstract available.

  PMID: 6448643 BACKGROUND

• Despotis GJ, Santoro SA, Spitznagel E, Kater KM, Cox JL, Barnes P, Lappas DG. Prospective evaluation and clinical utility of on-site monitoring of coagulation in patients undergoing cardiac operation. J Thorac Cardiovasc Surg. 1994 Jan;107(1):271-9.

  PMID: 8283896 BACKGROUND

• Lemmer JH Jr, Stanford W, Bonney SL, Breen JF, Chomka EV, Eldredge WJ, Holt WW, Karp RB, Laub GW, Lipton MJ, et al. Aprotinin for coronary bypass operations: efficacy, safety, and influence on early saphenous vein graft patency. A multicenter, randomized, double-blind, placebo-controlled study. J Thorac Cardiovasc Surg. 1994 Feb;107(2):543-51; discussion 551-3.

  PMID: 7508070 BACKGROUND

• Santos AT, Kalil RA, Bauemann C, Pereira JB, Nesralla IA. A randomized, double-blind, and placebo-controlled study with tranexamic acid of bleeding and fibrinolytic activity after primary coronary artery bypass grafting. Braz J Med Biol Res. 2006 Jan;39(1):63-9. doi: 10.1590/s0100-879x2006000100007. Epub 2005 Dec 15.

  PMID: 16400465 BACKGROUND

• Pleym H, Stenseth R, Wahba A, Bjella L, Karevold A, Dale O. Single-dose tranexamic acid reduces postoperative bleeding after coronary surgery in patients treated with aspirin until surgery. Anesth Analg. 2003 Apr;96(4):923-928. doi: 10.1213/01.ANE.0000054001.37346.03.

  PMID: 12651635 BACKGROUND

• Myles PS, Smith JA, Forbes A, Silbert B, Jayarajah M, Painter T, Cooper DJ, Marasco S, McNeil J, Bussieres JS, McGuinness S, Byrne K, Chan MT, Landoni G, Wallace S; ATACAS Investigators of the ANZCA Clinical Trials Network. Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery. N Engl J Med. 2017 Jan 12;376(2):136-148. doi: 10.1056/NEJMoa1606424. Epub 2016 Oct 23.

  PMID: 27774838 BACKGROUND

• Martin K, Wiesner G, Breuer T, Lange R, Tassani P. The risks of aprotinin and tranexamic acid in cardiac surgery: a one-year follow-up of 1188 consecutive patients. Anesth Analg. 2008 Dec;107(6):1783-90. doi: 10.1213/ane.0b013e318184bc20.

  PMID: 19020118 BACKGROUND

• Kalavrouziotis D, Voisine P, Mohammadi S, Dionne S, Dagenais F. High-dose tranexamic acid is an independent predictor of early seizure after cardiopulmonary bypass. Ann Thorac Surg. 2012 Jan;93(1):148-54. doi: 10.1016/j.athoracsur.2011.07.085. Epub 2011 Nov 4.

  PMID: 22054656 BACKGROUND

MeSH Terms

Conditions

Hemorrhage; Blood Loss, Surgical

Interventions

Tranexamic Acid

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intraoperative Complications

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Limitations and Caveats

Due to the small sample size (N\<100 patients) the DEPOSITION pilot trial is not sufficiently powered to detect statistically significant differences between topical and intravenous TxA groups.

Results Point of Contact

• Title: Research assistant
• Organization: Population Health Research Institute

Austin.Browne@phri.ca

19055212100

Study Officials

• Andre Lamy, MD MHSc

  Population Health Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The pharmacy will prepare 1 syringe of 50 ml of topical TA (5 g) or placebo. They will also prepare for the same patient 2 syringes of 50 ml (5 g) for intravenous (i.v.) injection or placebo. TA is similar in all aspects to normal saline. Blinding of both teams will be easy. The syringes will be prepared and randomized in pharmacy before the surgery.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Tranexamic Acid intravenous + Placebo topical versus Placebo intravenous + Tranexamic Acid topical

Study Record Dates

• First Submitted: November 17, 2017
• First Posted: December 18, 2017
• Study Start: December 21, 2017
• Primary Completion: September 4, 2018
• Study Completion: September 4, 2018
• Last Updated: February 11, 2021
• Results First Posted: September 9, 2019

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)