High vs Low Dose Dexamethasone on Complications in the Immediate Postoperative Phase After Mastectomy (DEX-MAS)

Effect of High vs Low Dose Intravenous Dexamethasone on Complications in the Immediate Postoperative Phase After Mastectomy- a Randomized, Double-blind, Controlled Trial

The aim of this study is to investigate the effect of a single preoperative high-dose steroid injection on complications in the immediate postoperative phase after breast cancer surgery, with removal of the breast (mastectomy). Primary outcome is the proportion patients who require transfer to the post anaesthesia care unit (PACU) and the proportion that can be transferred directly to the ward. Secondary outcomes are organospecific complications in the postanesthesia phase, pain and nausea the first 5 days, seroma and wound infection the first 14 days and readmissions the first 30 days after surgery.

The investigators hypothesize that the frequency of transfer to the PACU and organospecific complications will be lower among patients receiving high dose dexamethasone. The investigators hypothesize, that there will be no difference in wound infections, seroma or readmissions.

Study Overview

• Status: Completed
• Conditions: Systemic Inflammatory Response Syndrome; Pain, Postoperative; Postoperative Complications; Breast Cancer; Mastectomy; Dexamethasone; Nausea and Vomiting, Postoperative; Glucocorticoids; Steroid
• Intervention / Treatment: Drug: Dexamethasone

Detailed Description

Post-surgery, patients are traditionally observed and treated in post-anesthesia care units (PACU) until they are discharged to the ward (or directly home) assessed by standardized international discharge criteria.

The research project "Why in PACU?" (Rigshospitalet, Denmark), has since the beginning of 2016 systematically collected and analyzed procedure-related complications in the recovery phase. The complications include pain, nausea/vomiting, circulatory and respiratory problems, orthostatic intolerance and cognitive disorders. Common to all the above-mentioned post-operative problems are the possible links to the inflammatory response caused by the surgical trauma.

Glucocorticoids can in this context be central for the reduction of acute postoperative organ dysfunctions, caused by the anti-inflammatory effect. In a number of different surgical procedures, single dose, pre-operative glucocorticoids have been shown to reduce post-operative nausea and vomiting (PONV), acute pain and need of opioids as well as accelerate the convalescence.

Meta-analyses also showed that single-dose administration of glucocorticoids (methylprednisolone and dexamethasone) for surgical patients is safe as opposed to long-term treatment.

Based on positive results in other procedure-specific studies, all mastectomy patients at Rigshospitalet, have received pre-operative high-dose steroids, in the form of 24 mg dexamethasone injection since mid-2015. This has resulted in a decrease in the proportion of patients who need observation in PACU from 30 % to 10 %. The reduction is primarily due to less pain, less sedation, and lower opioid administration.

Whether this is also partly due to a "systemic effect" (Hawthorn effect) as a result of increased focus on the area cannot be excluded.

Prior to creating clinical recommendations and standards, it is required that the results be tested in a randomized, controlled, clinical trial.

The study is not placebo-controlled since the positive effects of dexamethasone 8 mg on PONV have been shown in numerous trials, and is already being administered to all patients at the clinic. It would therefore not be ethically correct to withdraw from this practise.

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• planned unilateral mastectomy with or without axillary dissection or sentinel node in the study period
• informed signed consent

Exclusion Criteria:

• Chronic/ongoing use of glucocorticoids (except inhalation therapy)
• ongoing use of immunosuppressive therapy
• insulin dependent diabetes
• pregnancy/breastfeeding
• allergies toward study medication, or medication in a standard treatment
• contralateral surgery (lumpectomy/mastectomy) at time of mastectomy
• surgery cannot be performed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dexamethasone 8 mg; Dexamethasone 8 mg pre-operative	Drug: Dexamethasone; pre-operative intravenous administration
Active Comparator: Dexamethasone 24 mg; Dexamethasone 24 mg pre-operative	Drug: Dexamethasone; pre-operative intravenous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transfer to Post-anesthesia Care Unit (PACU)	Number of patients meeting criteria for transfer to PACU post-surgery	Within 1 hour post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Discharge Score,(Modified Aldrete Discharge Score), Operating Room	Danish Society of Anesthesiology and Intensive Care Medicine (DASAIM) discharge score.Construct: The score consists of six modalities (subscores): Sedation,Oxygen saturation,blood pressure,heart rate,pain (at rest)and nausea.Each modality has a score between 0 and 3,and patients are considered dischargeable to the ward when the score sum of all criteria (total score) is 4 or less and no single score is above 1. All values (subscores) are considered best at 0 and worst at 3. Sedation: 0 fully awake, 1, sleeping aroused by verbal stimuli, 2 sleeping aroused by physical stimuli, 3 sleeping cannot be aroused. Oxygen saturation (%):0 ≥94, 1 90-93, 2 85-89, 3 <85. Blood pressure, systolic (mmHg): 0 100-220, 1 90-99. 2 80-89 or >220, 3<80. Heart rate; pr. min: 0 50-100, 1 101-120, 2 40-49 or 121-130, 3 <40 or >130. Pain (at rest) (Numeric rating scale 0-10): 0 0, 1 0-2, 2 3-6, 3 ≥ 7 Nausea (patient evaluation and nurse observation): 0 none, 1 light, 2 moderate, 3 severe or vomiting.	At transfer from operating room, within 1 hour post-surgery
Discharge Score, Arrival at PACU	DASAIM score (Danish Society of Anesthesiology and Intensive Care Medicine). The score consists of six modalities: Sedation, Oxygen saturation, blood pressure, heart rate, pain (at rest) and nausea. Each modality has a score between 0 and 3, and patients are considered dischargeable to the ward when the score sum of all criteria is four or less and no single score is above one. Sedation: 0 fully awake, 1, sleeping aroused by verbal stimuli, 2 sleeping, aroused by physical stimuli, 3 sleeping, cannot be aroused. Oxygen saturation (%): 0 ≥ 94, 1 90-93, 2 85-89, 3 <85. Blood pressure, systolic (mmHg): 0 100-220, 1 90-99. 2 80-89 or >220, 3<80. Heart rate; pr. min: 0 50-100, 1 101-120, 2 40-49 or 121-130, 3 <40 or >130. Pain (at rest) (Numeric rating scale 0-10): 0 0, 1 0-2, 2 3-6, 3 ≥ 7 Nausea (patient evaluation and nurse observation): 0 none, 1 light, 2 moderate, 3 severe or vomiting.	within 3 hours
Discharge Score, Arrival at Ward	DASAIM score (Danish Society of Anesthesiology and Intensive Care Medicine). The score consists of six modalities: Sedation, Oxygen saturation, blood pressure, heart rate, pain (at rest) and nausea. Each modality has a score between 0 and 3, and patients are considered dischargeable to the ward when the score sum of all criteria is four or less and no single score is above one. Sedation: 0 fully awake, 1, sleeping aroused by verbal stimuli, 2 sleeping, aroused by physical stimuli, 3 sleeping, cannot be aroused. Oxygen saturation (%): 0 ≥ 94, 1 90-93, 2 85-89, 3 <85. Blood pressure, systolic (mmHg): 0 100-220, 1 90-99. 2 80-89 or >220, 3<80. Heart rate; pr. min: 0 50-100, 1 101-120, 2 40-49 or 121-130, 3 <40 or >130. Pain (at rest) (Numeric rating scale 0-10): 0 0, 1 0-2, 2 3-6, 3 ≥ 7 Nausea (patient evaluation and nurse observation): 0 none, 1 light, 2 moderate, 3 severe or vomiting.	within 3 hours
Number of Participants With Complication	complications requiring treatment until discharge	24 hours
Total Length of Stay in PACU	Length of stay in the post-anesthesia care unit (PACU), measured as hours and minutes, from start of procedure, to discharge from PACU	12 hours
Total Length of Stay in Hospital	Length of stay in hospital, measured from start of procedure to discharge from hospital to home	24-48 hours
Secondary Transfer	Secondary transfer to PACU from ward, or to intensive care unit from PACU	24-48 hours
Pain, Numeric Rating Scale	Self-reported pain (worst and average (average through that day), days 0-4) on a numeric rating scale (NRS) 0-10. 0 is no pain, 10 is worst pain imaginable.. Questionnaire.	days 0-4
Post Operative Nausea and Vomiting (PONV).	Self-reported nausea, questionnaire, day 0-4. Number of participants reporting nausea and/or vomiting	days 0-4
Quality of Sleep	Self-reported quality of sleep (days 0-4). Questionnaire. Dichotomized to Good sleep or sleep problems, numbers reported are number of patients with sleep problems	days 0-4
Mental Status	Self-reported feelings of restlessness, sadness and fatigue (days 0-4). Questionnaire (anwers possible: yes or no. Numbers are patients answering yes)	days 0-4
Number of Participants With Seroma, Requiring Treatment	Seroma, requiring treatment the first 14 days.	14 days
Readmission	Any readmission, days 0-30	30 days

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Investigators: Principal Investigator: kristin J Steinthorsdottir, MD, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2017
• Primary Completion (Actual): April 22, 2018
• Study Completion (Actual): April 22, 2018

Study Registration Dates

• First Submitted: March 28, 2017
• First Submitted That Met QC Criteria: April 19, 2017
• First Posted (Actual): April 24, 2017

Study Record Updates

• Last Update Posted (Actual): December 2, 2019
• Last Update Submitted That Met QC Criteria: November 27, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Pain; Neurologic Manifestations; Signs and Symptoms, Digestive; Shock; Nausea; Pain, Postoperative; Vomiting; Postoperative Complications; Postoperative Nausea and Vomiting; Systemic Inflammatory Response Syndrome; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: DEXMAS01; 2017-000227-27 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Not planned to share IPD

Drug and device information, study documents

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