Preoperative Methylprednisolone to Patients Suspected of Appendicitis Undergoing Laparoscopy

To test whether 125 mg preoperative methylprednisolone intravenously can reduce postoperative pain after laparoscopy for suspected appendicitis and to test whether preoperative methylprednisolone can reduce postoperative fatigue, increase quality of sleep, reduce nausea or vomiting, reduce duration of convalescence and increase overall quality of recovery after laparoscopy for suspected appendicitis.

Study Overview

• Status: Completed
• Conditions: Suspected Appendicitis
• Intervention / Treatment: Drug: Methylprednisolone; Drug: 0.9% Saline

Detailed Description

Patients enrolled are randomized to active substance or placebo approximately 30 minutes prior to skin incision.

Patients are followed for 30 days postoperative with registration of outcomes on a postoperative questionnaire. Patients are contacted by telephone at every registration time. The primary outcome is also secured over the telephone in case patients do not return their questionnaire.

With a power of 80% and a significance level of 5% we need 64 patients (32 in each arm) to show a 30% reduction in postoperative pain during the first 3 postoperative days with 5 measurements and we need 42 patients (21 in each arm) to show a 15% increase in the QoR-15 during the first 3 postoperative days. With an anticipated loss to follow up of 20% we need 80 patients ( 40 in each arm).

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Hillerød, Denmark
    • Nordsjaellands Hospital
  • Køge, Denmark
    • Køge Sygehus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Laparoscopy for suspected appendicitis
• Age 18 years or older
• American Society of Anesthesiologist (ASA) class I-III.
• Gives written and oral consent

Exclusion Criteria:

• Known inflammatory bowel disease.
• Known autoimmune disease.
• Chronic pain patient.
• Presumed poor compliance.
• Pregnant or breastfeeding.
• In systematic treatment with glucocorticoids or other immunosuppressive treatment.
• Known renal disease, GFR<30.
• Known liver cirrhosis.
• Known heart failure, EF<40%.
• Known glaucoma.
• Known ocular herpes simplex.
• Known cushings disease.

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
Experimental: Methylprednisolone; 125 mg Methylprednisolone intravenously approximately 30 minutes prior to skin incision	Drug: Methylprednisolone; 125 mg methylprednisolone as an intravenously bolus injection approximately 30 minutes prior to skin incision.; Other Names: Solu-Medrol
Placebo Comparator: Placebo; 0.9% Saline intravenously approximately 30 minutes prior to skin incision	Drug: 0.9% Saline; 0,9% Saline as an intravenously bolus injection approximately 30 minutes prior to skin incision.; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain at rest during the first 3 postoperative days on a 11-point NRS	Powered to detect 30% reduction, Random regression model (mixed effects model)	6 hours, 12 hours, postoperative day (POD) 1, POD2 and POD3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain when coughing during the first 3 postoperative days on a 11-point NRS	Random regression model (mixed effects model)	6 hours, 12 hours, postoperative day (POD) 1, POD2 and POD3
Fatigue during the first 3 postoperative days on a 11-point NRS	Random regression model (mixed effects model)	6 hours, 12 hours, postoperative day (POD) 1, POD2 and POD3
Sleep during the first 3 postoperative days on a 11-point NRS		postoperative day (POD) 1, POD2 and POD3
QoR-15 during the first 3 postoperative days	Powered to detect 15% increase,	postoperative day (POD) 1, POD2 and POD3
Incidence of postoperative nausea or vomiting during the first postoperative day		6 hours, 12 hours and 24-32 hours postoperative
Pain at rest after POD3 on a 11-point NRS		postoperative day (POD) 7, POD 14 and POD 30
Pain when coughing after POD3 on a 11-point NRS		postoperative day (POD) 7, POD 14 and POD 30
Fatigue after POD3 on a 11-point NRS		postoperative day (POD) 7, POD 14 and POD 30
Sleep after POD3 on a 11-point NRS		postoperative day (POD) 7, POD 14 and POD 30
QoR-15 after POD 3		postoperative day (POD) 7, POD 14 and POD 30
Mobilization during the first postoperative day on a 4-point likert scale		6 hours, 12 hours and postoperative day 1
Resumption of occupational activity	Number of days from surgery until resumption of occupational activities	Up to 60 days postoperative
Resumption of recreational activity	Number of days from surgery until resumption of recreational activities	Up to 60 days postoperative
Duration of convalescence	Number of days from surgery until resumption of both occupational and recreational activities	Up to 60 days postoperative
Adverse events according to GCP guidelines		30 day postoperative
Postoperative complications according to the Clavien-Dindo classification		30 day postoperative
Opioid consumption during the first 24 hours postoperative	Both as a the need for opioids and the amount equivalent to intravenous morphine.	24 hours postoperative
Need for rescue antiemetics during the first 24 hours postoperative		24 hours postoperative
Duration of postoperative hospital stay	The duration of the postoperative hospital stay in hours.	30 days postoperative

Collaborators and Investigators

• Sponsor: Jakob Kleif
• Collaborators: Zealand University Hospital
• Investigators: Principal Investigator: Jakob Kleif, M.D., Nordsjaellands Hospital

Publications and helpful links

General Publications

• Kleif J, Gogenur I. Severity classification of the quality of recovery-15 score-An observational study. J Surg Res. 2018 May;225:101-107. doi: 10.1016/j.jss.2017.12.040. Epub 2018 Feb 21.
• Kleif J, Hauge CI, Vilandt J, Gogenur I. Randomized Clinical Trial of Preoperative High-Dose Methylprednisolone on Postoperative Pain at Rest After Laparoscopic Appendectomy. Anesth Analg. 2018 May;126(5):1712-1720. doi: 10.1213/ANE.0000000000002693.

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: February 23, 2016
• First Submitted That Met QC Criteria: March 16, 2016
• First Posted (Estimate): March 17, 2016

Study Record Updates

• Last Update Posted (Estimate): September 27, 2016
• Last Update Submitted That Met QC Criteria: September 24, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: laparoscopy; acute surgery
• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Cecal Diseases; Intraabdominal Infections; Appendicitis; 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; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: 2015-810; 2015-004800-46 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided