Perianal Abscess Recurrence and Fistula Formation: Antibiotics Following Incision and Drainage Trial (PARFAIT)

Perianal Abscess Recurrence and Fistula Formation: Antibiotics Following Incision and Drainage Trial - (PARFAIT) A Vanguard Randomized Controlled Trial

Most perianal abscesses (PA) result from an infection originating in anal crypts that extend into anal glands in the intersphincteric plane. Patients commonly present to the ER and usually require surgical intervention, which poses a burden on the healthcare system. If left undrained, a PA can expand into the adjacent tissues as well as progress to systemic infection. One of the major complications of PA are perianal fistulae; the creation of a tract between the anal canal and the perianal skin that is lined with granulation tissue or skin cells. Up to 1/3 of patients with a PA will develop a fistula; which occurs if a PA drains spontaneously through the perianal skin, and the infection becomes chronic. If this happens, surgical intervention is needed and abscesses may reoccur. Post incision and drainage (I&D) antibiotics in PA have been used to address complications but their use is still controversial and there are no specific recommendations on their use to prevent the formations of fistulae.

Recent findings from a systematic review (6 studies, N=817 patients) published in 2019 demonstrated that antibiotic use following I&D of PA was associated with a 36% lower odds of fistula formation, though the quality of the evidence was low.

As there are no established prophylactic treatments for fistulae, and because they are difficult to treat, further study of this simple intervention seems warranted. In this trial, adults with a PA requiring I&D will be randomly assigned to receive standard of care with antibiotics or standard of care without antibiotics after I&D. This trial will be conducted under the IMPACTS (Innovative, Multicentre, Patient-centred Approach to Clinical Trials in Surgery) program umbrella and will follow IMPACTS methodology. For the Vanguard trial, the aim is to determine the feasibility of conducting a definitive trial. Future outcomes of interest are incidence of fistula formation (defined as drainage of the perianal region at or after 2 months), need for re-intervention (i.e., any intervention on the perianal region), quality of life, healthcare utilization, healing time and mortality.

Study Overview

• Status: Active, not recruiting
• Conditions: Perianal Abscess; Perianal Fistula
• Intervention / Treatment: Drug: Antibiotic 1 arm (amoxicillin + clavulanic acid); Drug: Antibiotic 2 arm (ciprofloxacin + metronidazole)

Detailed Description

The development of perianal abscesses is relatively common with an estimated incidence in the UK of 40 per 100,000 habitants (Canadian incidence unknown). It is uncertain if there is any benefit to using prophylactic antibiotics after incision and drainage of a perianal abscess in order to reduce the formation of fistulae, the need for re-intervention, health system costs, and healing time. Further research from high-quality RCTs is needed to establish a benefit, if any, for this practice.

Objectives: Before embarking on a definitive RCT, this pilot trial has five specific feasibility objectives:

1. To assess our ability to accrue patients using the IMPACTS Program design platform at multiple institutions, over the course of one year.
2. To assess our ability to adaptively randomize patients and deliver the randomized assignment using the IMPACTS Program design platform, over the course of one year.
3. To assess our ability to collect complete data directly from participants (patients and clinicians) on: re-intervention, fistula formation, quality of life, and healing time over the course of one year.
4. To examine our ability to carry out data linkages using the IMPACTS Program design platform over the course of one year.
5. To estimate the incidence of fistula formation to inform the sample size calculation for the definitive trial.

Study design: This is a multicentre, pragmatic, open label, three-arm parallel-group Vanguard feasibility randomized controlled trial. Adult patients with perianal abscesses requiring incision and drainage will be randomized to receive standard of care with antibiotics or standard of care without antibiotics after incision and drainage. If feasibility is demonstrated during the pilot trial, we will plan to conduct a definitive trial. If there are only minimal changes to the protocol, we will include data from the pilot phase into the definitive trial analysis (i.e. a Vanguard design).

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • North York, Ontario, Canada, M2K 1E1
      • North York General Hospital
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients aged ≥18 years
• Perianal abscess requiring incision and drainage

Exclusion Criteria:

• Allergies or contraindications to amoxicillin + clavulanic acid, penicillin, ciprofloxacin, or metronidazole
• Definite need to be on antibiotics at the treating clinicians' discretion
• Immunosuppression such as: human immunodeficiency virus (HIV), chronic steroids treatment, current chemotherapy
• Abscess associated with Inflammatory Bowel Disease (IBD)
• Supralevator perianal abscess
• Recurrent perianal abscesses within 5 years
• Known rectal cancer diagnosis within 5 years
• History of pelvic radiotherapy within 5 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Antibiotic 1 arm (amoxicillin + clavulanic acid); Patients will undergo I&D of PA by the clinician as per standard of care. This may occur in the emergency department or operating room. Patients may or may not receive packing based on the clinician's standard practice and institutional routines. Patients randomized to the antibiotic 1 arm will receive a prescription for amoxicillin + clavulanic acid (875 mg amoxicillin and 125 mg clavulanic acid BID) PO for 7 days. Otherwise, all participants will be treated identically according to the institution's standard practices.	Drug: Antibiotic 1 arm (amoxicillin + clavulanic acid); Prescription of antibiotics (amoxicillin + clavulanic acid) after incision and drainage of perianal abscess.
Active Comparator: Antibiotic 2 arm (ciprofloxacin + metronidazole); Patients will undergo I&D of PA by the clinician as per standard of care. This may occur in the emergency department or operating room. Patients may or may not receive packing based on the clinician's standard practice and institutional routines. Patients randomized to the antibiotic 2 arm will receive a prescription for ciprofloxacin + metronidazole (ciprofloxacin 500 mg and metronidazole 500 mg BID) PO for 7 days. Otherwise, all participants will be treated identically according to the institution's standard practices.	Drug: Antibiotic 2 arm (ciprofloxacin + metronidazole); Prescription of antibiotics (ciprofloxacin + metronidazole) after incision and drainage of perianal abscess.
No Intervention: No antibiotics; Patients will undergo I&D of PA by the clinician as per standard of care. This may occur in the emergency department or operating room. Patients may or may not receive packing based on the clinician's standard practice and institutional routines. In the comparator arm, patients will not receive any antibiotics. Otherwise, all participants will be treated identically according to the institution's standard practices.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants who received the allocated intervention, across all sites	Feasible if >90% of patients receive correct intervention	1 year
Proportion of complete data collection for patient-reported outcome surveys, across all sites	Feasible if >80% of data is collected	1 year
Total number of participants accrued across all sites, per month	Feasible if 3 or more patients accrued per month between all sites	1 year
Proportion of successful data linkage of patient-reported outcome data with Institute of Clinical Evaluative Sciences dataset(s)	Feasible if linkage is possible in >90% of patients	1 year
Estimation of fistula formation in three groups	Rate of fistula formation in the three groups	1 year

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Investigators: Principal Investigator: Paul Karanicolas, MD PhD, Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2021
• Primary Completion (Actual): October 31, 2022
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: September 8, 2020
• First Submitted That Met QC Criteria: September 8, 2020
• First Posted (Actual): September 16, 2020

Study Record Updates

• Last Update Posted (Estimated): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Post-operative antibiotics
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Inflammation; Disease Attributes; Pathological Conditions, Anatomical; Suppuration; Recurrence; Fistula; Abscess; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antitubercular Agents; Cytochrome P-450 CYP1A2 Inhibitors; beta-Lactamase Inhibitors; Metronidazole; Anti-Bacterial Agents; Antibiotics, Antitubercular; Ciprofloxacin; Amoxicillin; Clavulanic Acid; Clavulanic Acids; Amoxicillin-Potassium Clavulanate Combination
• Other Study ID Numbers: CTO Project ID: 2122

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