The Effect of Topical Administration of Common Drugs on Postoperative Bleeding and Pain

The Effect of Topical Administration of Tranexamic Acid, Adrenaline and Bupivacain on Postoperative Bleeding and Pain in Patients Undergoing Breast Surgery. A Four-armed Placebo-controlled Double Blinded Randomized Study

After surgical procedures, interventions to reduce postoperative pain and bleeding are of great importance. In this study, the effect will be investigated of smearing common drugs, which are designed for injection, directly onto the raw wound surface (topical application) created during surgery. Topical application allows a small amount of drug to reach a large wound area, higher drug concentration in the exposed wound surface but very low concentration in the body, and no risk of injury from needles. Although beneficial effects of such an easy and low-cost intervention would be expected, the investigators have found no previous reports on blinded and controlled studies.

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative; Postoperative Hemorrhage
• Intervention / Treatment: Drug: saline; Drug: Tranexamic Acid; Drug: Adrenaline; Drug: Bupivacaine; Drug: tranexamic acid plus saline

Detailed Description

The drugs to be studied on whether they reduce bleeding are adrenaline (constricts blood vessels) and tranexamic acid (TXA) (prevents bloodclots from dissolving). The drug studied to what extent it reduces pain will be bupivacaine, a common local anaesthetic. Patients undergoing bilateral symmetric breast surgery or single sided mastectomies are candidates for enrollment in the study. The bilateral patients will have two identical procedures and hence two identical wounds in the same patient. This enables the investigators to use one side as control and hence design our study arms as prospective and placebo-controlled. The patients undergoing a one-sided procedure will need to be compared to similar patients, but as wounds will be of different sizes and in different people, larger groups are needed to find significant differences between treatment and controls.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Norway
  • Trondheim, Norway, 7006
    • St Olavs University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patients undergoing unilateral simple mastectomy
• patients undergoing bilateral symmetric breast surgery

Exclusion Criteria:

• pregnancy
• A history of former thromboembolic events (to receive TXA)
• cardiovascular disease (to receive adrenaline)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: topical tranexamic acid; tranexamic acid to be smeared on surgical wounds before closure	Drug: Tranexamic Acid; Topical administration - does it reduce surgical bleeding?
Experimental: topical adrenaline; adrenaline solution to be smeared on surgical wounds before closure	Drug: Adrenaline; Topical adrenaline - does it reduce bleeding on its own, and does it enhance the effect of tranexamic acid?
Experimental: topical bupivacaine; bupivacaine to be smeared on surgical wounds before closure	Drug: Bupivacaine; Topical Bupivacaine- does it reduce surgical pain?; Other Names: Marcaine
Experimental: topical adrenaline plus tranexamic acid; tranexamic acid and adrenaline to be smeared on surgical wounds before closure	Drug: Tranexamic Acid; Topical administration - does it reduce surgical bleeding?; Drug: Adrenaline; Topical adrenaline - does it reduce bleeding on its own, and does it enhance the effect of tranexamic acid?
Placebo Comparator: placebo control; saline to be smeared on surgical wounds before closure	Drug: saline
Placebo Comparator: tranexamic acid and placebo control; tranexamic acid and saline to be smeared on surgical wounds before closure	Drug: tranexamic acid plus saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amount of blood on drains postoperatively	Drains are placed in surgical wounds during operation, and amount of blood on drains measured in ml on the control after 24 hours.	24 hours postoperatively
Amount of pain in operated breast	Evaluate using a visual analogue scale the pain in the surgical wounds as reported by the patient 24 hours postoperatively	Measured 24 hours postoperatively

Collaborators and Investigators

• Sponsor: St. Olavs Hospital
• Investigators: Study Director: Hilde Pleym, MD PhD, St. Olavs Hospital

Publications and helpful links

General Publications

• Ausen K, Fossmark R, Spigset O, Pleym H. Randomized clinical trial of topical tranexamic acid after reduction mammoplasty. Br J Surg. 2015 Oct;102(11):1348-53. doi: 10.1002/bjs.9878.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2013
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: October 10, 2013
• First Submitted That Met QC Criteria: October 14, 2013
• First Posted (Estimate): October 17, 2013

Study Record Updates

• Last Update Posted (Actual): May 17, 2019
• Last Update Submitted That Met QC Criteria: May 16, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: surgery; bupivacaine; tranexamic acid; Administration, topical; adrenaline
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Hemorrhage; Postoperative Hemorrhage; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Fibrin Modulating Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Anesthetics, Local; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Tranexamic Acid; Bupivacaine; Epinephrine; Racepinephrine; Epinephryl borate
• Other Study ID Numbers: 2012-004964-23 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No