Does Additional Use of Preoperative Azithromycin Decrease Posthysterectomy Infections

Infections After Hysterectomy - a Placebo-controlled Study Comparing the Prophylactic Use of Azithromycin and Cefuroxime With Single Cefuroxime

During hysterectomy bacteria may enter into the peritoneal cavity through vaginal opening and contaminate the healing tissues. The risk for deep infection after hysterectomy is about 5%. By reducing post-hysterectomy infections, it is possible to reduce individual burden of disease in addition to the direct and indirect financial costs. This study primary aim is to assess if prophylactic preoperative use of azithromycin in addition to generally used cefuroxime decreases post-hysterectomy infections as compared to cefuroxime only prophylaxis during 30 days after hysterectomy. Secondary aim is to assess if there is change in post-hysterectomy superficial infections, urinary tract infections, or post-operative fever between the cohorts and to report possible side-effects of the used antibiotics. In addition, the study finds out a possible role of bacterial vaginosis and microbiome n post-hysterectomy infections.

Study Overview

• Status: Recruiting
• Conditions: Hysterectomy; Antibiotics; Infection Post Op; Prophylactic
• Intervention / Treatment: Drug: Azithromycin Pill + Cefuroxime; Drug: Placebo + Cefuroxime

• Study Type: Interventional
• Enrollment (Estimated): 2278
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Päivi K Rahkola-Soisalo, Adj prof,MD; Phone Number: +358504270411; Email: paivi.rahkola-soisalo@hus.fi
• Study Contact Backup: Name: Ninja Savonius, MD; Phone Number: +358503466986; Email: ninja.savonius@hus.fi

Study Locations

• Finland
  • Helsinki, Finland
    • Recruiting
    • Helsinki University Central Hospital
    • Contact: Ninja Savonius, MD; Phone Number: +358503466986; Email: ninja.savonius@hus.fi
    • Contact: Päivi K Rahkola-Soisalo, Adj prof,MD; Phone Number: +358 50 4270411; Email: paivi.rahkola-soisalo@hus.fi
    • Sub-Investigator: Liisu Saavalainen, PhD, MD
    • Sub-Investigator: Päivi Härkki, Adj prof, MD
    • Sub-Investigator: Tomi Mikkola, Prof, MD
    • Sub-Investigator: Veli-Jukka Anttila, Adj prof,MD
    • Sub-Investigator: Seppo Virtanen, DI, MD
    • Sub-Investigator: Anne Saloranta, Adj Prof
    • Sub-Investigator: Ilkka Kalliala, Adj Prof, MD
    • Sub-Investigator: Suvi Niku, PhD, MD
  • Kuopio, Finland, 70029
    • Recruiting
    • Kuopio University Central Hospital
    • Contact: Henna Kärkkäinen, PhD; Phone Number: +358 44 7172741; Email: henna.karkkainen@kuh.fi
  • Oulu, Finland, PL23
    • Recruiting
    • Oulu University Central Hospital
    • Contact: Sari Koivurova, PhD; Phone Number: +358 8 3150211; Email: sari.koivurova@ppshp.fi
  • Tampere, Finland, 33521
    • Recruiting
    • Tampere University Central Hospital
    • Contact: Riikka Niemi, PhD; Phone Number: +358 3 31169083; Email: riikka.niemi@pshp.fi
    • Sub-Investigator: Elina Ylilehtot, PhD, MD
  • Turku, Finland
    • Not yet recruiting
    • Turku University Central Hospital
    • Contact: Pia Heinonen, PhD; Phone Number: +358 2 313 5002; Email: pia.heinonen@tyks.fi

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Women undergoing hysterectomy for benign indication in University Hospitals (Helsinki University Hospital, Turku University Hospital, Tampere University Hospital, Oulu University Hospital and Kuopio University Hospital) who have not any contraindications for azithromycin or cefuroxime.

Exclusion Criteria:

• Inability to understand the study protocol.
• Allergy for either cefuroxime or azithromycin.
• Congenital or acquired prolonged Q-T-corrected interval. All the participants will be asked about arrhythmias and whether they have congenital arrhythmias in the family,
• Electrocardiogram will be checked for all the participants.
• Use of medicines that may prolong Q-T-corrected interval (class Ia arrhythmia medications, quinidine, procainamide, and class III arrhythmia medications dofetilide, amiodarone and sotalol).
• Use of selective serotonin reuptake inhibitor medication and prolonged Q-T-corrected interval.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Azithromycin + Cefuroxime; Changed with renewed study permissions: These patients will receive Azithromycin 500 mg (2 tablets) per orally on the operation day when they arrive to the hospital and a single dose Cefuroxime 1.5g (when body mass index is under 30) or 3g (for those whose bosy mass index is 30 or more) in the operating theatre before the incision. The previous description: These patients will receive Azithromycin 500 mg (2 tablets) per orally in the evening before the operation and single dose Cefuroxime 1.5g (when body mass index is under 30) or 3g (for those whose body mass index is 30 or more) in the operating theatre before the incision.	Drug: Azithromycin Pill + Cefuroxime; Azithromycin 500 mg (2 tablets) per orally when arriving to the hospital before the operation and a single dose Cefuroxime 1.5g (when body mass index is under 30) or 3g (for those whose body mass index is 30 or more) in the operating theatre before the incision
Active Comparator: Placebo + Cefuroxime; Changed with new study permissions: These patients will receive placebo (2 tablets) per orally on the operation day when they arrive to the hospital and a single dose Cefuroxime 1.5g (when body mass index is under 30) or 3g (for those whose bosy mass index is 30 or more)in the operating theatre before the incision. The previous description: These patients will receive placebo (2 tablets) per orally in the evening before the operation and a single dose Cefuroxime 1.5g (when body mass index is under 30) or 3g (for those whose body mass index is 30 or more) in the operating theatre before the incision.	Drug: Placebo + Cefuroxime; Placebo (2 tablets) per orally in the evening when arriving to the hospital before the operation and a single dose Cefuroxime 1.5g (when body mass index is under 30) or 3g (for those whose body mass index is 30 or more) in the operating theatre before the incision

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of post-hysterectomy episodes with deep infections	Number of deep wound and pelvic organ infection episodes reported by patients and doctors	Deep infections that occur between the first and 30th postoperative day after hysterectomy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of other post-hysterectomy infections or fever episodes	Number of superficial infections, other infections, such has urine tract infections, or fever episodes lasting over 38 ℃ over 2 days	Number of other infections or fever episodes that occur between the first and 30th postoperative day after hysterectomy.

Collaborators and Investigators

• Sponsor: Helsinki University Central Hospital
• Collaborators: University of Turku; Oulu University Hospital; Kuopio University Hospital; Tampere University Hospital
• Investigators: Principal Investigator: Päivi Rahkola-Soisalo, Adj prof, MD, Helsinki University Central Hospital; Study Chair: Tomi Mikkola, Prof, MD, Helsinki University Central Hospital; Study Director: Päivi Rahkola-Soisalo, Adj prof, MD, Helsinki University Central Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2022
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: April 14, 2022
• First Submitted That Met QC Criteria: April 14, 2022
• First Posted (Actual): April 20, 2022

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: November 13, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: postoperative, infection, hysterectomy, antibiotics
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Anti-Infective Agents; Anti-Bacterial Agents; Azithromycin; Cefuroxime; Cefuroxime axetil
• Other Study ID Numbers: HUS/117/2022; 2021-003467-10 (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