Clinical trial NCT05385887: Antibiotic Treatment foLlowing Surgical drAinage of Perianal abScess; the ATLAS Trial
Official title: Antibiotic Treatment foLlowing Surgical drAinage of Perianal abScess; the ATLAS Trial, a Double-blind, Placebo-controlled, Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Perianal Fistula
Perianal Abscess
Drain Abscess
Keywords: antibiotics
antibiotic treatment
perianal fistula
perianal abscess
drainage of abscess
Lead sponsor: Proctos Kliniek
Sponsor class: OTHER
Collaborators: name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
First posted: 2022-05-23
Enrollment: 298
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: double-blind, placebo-controlled, randomized trial
Primary purpose: TREATMENT

Brief summary: Rationale:

Perianal fistula is a burdening disease with an annual prevalence of 2/100.000 in the Dutch population. More than 90% of crypto-glandular fistulas originate from anorectal abscess. Despite adequate drainage of anorectal abscess up to 83% recurs or results in an anal fistula, the majority developing within 12 months. Up till now it is not common practice to routinely administer prophylactic antibiotics to prevent anal fistula development.\\

Objective:

The objective of this trial is to establish if adding antibiotic treatment to surgical drainage of perianal abscess results in less perianal fistulas.

Study design:

The study concerns a double-blind, placebo-controlled, randomized, multicenter trial with treatment of perianal abscess by surgical drainage alone or combined with antibiotic treatment. Patients will be accrued by all participating clinics. The design involves allocation of all appropriate consecutive patients with a primary occurrence of perianal abscess to surgical drainage followed by either antibiotics or placebo. Data will be analyzed on 'intention to treat' basis in case patients are not subjected to the randomized treatment modality.

Study population:

Men and women of 18 years and older who present for the first time with a perianal abscess.

Intervention (if applicable): The antibiotic group receives 7 days of oral metronidazole (500 mg every eight hours) and ciprofloxacin (500 mg every twelve hours) in addition to surgical drainage. The other group receives surgical drainage and postoperatively identical placebo tablets.

Main study parameters/endpoints:

Primary outcome measure is development of a perianal fistula. Secondary outcome measures are quality of life at 12 months measured with the EQ-5D-5L with Dutch rating. Further: in-hospital direct and indirect costs and out-of hospital postoperative costs, need of repeated drainage, patient related outcome (PRO) and clinical outcome measures.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

For this study, patients are asked to take part in a study comparing the addition of antibiotic treatment to surgical drainage of perianal abscess. Patients will not be burdened by extra hospital visits. At baseline participants will complete PRO questionnaires. Also at 1 week and 3, 6 and 12 months participants will fulfill the PRO questionnaires. These will be send to them by email and will take approximately 10 minutes each time.


Eligibility criteria: Inclusion Criteria:

* Men and women aged 18 years or older
* Eligible for e-mail questionnaires
* Sufficient understanding of the Dutch written language (reading and writing)
* Obtained written informed consent

Exclusion Criteria:

* A coexistent anorectal fistula
* Secondary or recurrent anorectal abscess
* Presence of an internal fistula opening
* Any additional surgical procedure performed during the same session
* Previous (peri)anal surgery
* Inflammatory bowel disease
* History of radiation of the pelvic area
* Anorectal malignancy
* Immunodeficiency
* Kidney failure (eGFR \<30ml/min)
* Valvular heart disease
* Pregnancy or lactation
* Postoperative antibiotic prophylaxis indicated for another reason
* Immunosuppressive medication at the time of surgery
* Allergy to metronidazole or ciprofloxacin
* Not able or trouble with swallowing pills
* Concomitant use of:

  * Tizanidine, theophylline, clozapine, olanzapine, pirfenidone, carbamazepine, agomelatine (these are all CYP1A2 substrates, ciprofloxacin is an inhibitor)
  * Amiodarone, erythromycin, sotalol, azithromycin, citalopram, escitalopram, flecainide, fluconazole, haloperidol \>5mg/day, methadone, ondansetron (concerning prolonged QT interval in combination with ciprofloxacin)
  * Lithium (can cause toxic levels with metronidazole)
  * Lopinavir/ritonavir, ritonavir capsules, temsirolimus, disulfiram (antabuse), mebendazole (can cause serious side effects, confusion and psychosis in combination with metronidazole)
  * Corticosteroids (in combination with ciprofloxacin higher risk of tendinitis and tendon rupture).

Primary outcomes:
measure: Perianal fistula at 1 year follow up
timeFrame: 1 year
Secondary outcomes:
measure: Quality of life at 12 months measured with the EQ-5D-5L with Dutch rating.
timeFrame: 1 year
measure: In-hospital direct and indirect costs and out-of hospital posteroperative costs
timeFrame: 1 year
measure: Need of repeated drainage
timeFrame: 1 year
measure: PROMs
timeFrame: 1 year
measure: Day of discharge from hospital
timeFrame: 1 year
measure: Postoperative complications
timeFrame: 1 year
measure: Recurrent abscess
timeFrame: 1 year
measure: Duration of absence from work
timeFrame: 1 year
Other outcomes:
Locations:
city: Tilburg
country: Netherlands
facility: Elisabeth-TweeSteden ziekenhuis
state: Noord-Brabant
city: Beverwijk
country: Netherlands
facility: Rode Kruis ziekenhuis
state: Noord-Holland
city: Breda
country: Netherlands
facility: Amphia hospital
state: North-Brabant
city: Amsterdam
country: Netherlands
facility: OLVG
state: North-Holland
city: Hoorn
country: Netherlands
facility: Dijklander hospital
state: North-Holland
city: Bilthoven
country: Netherlands
facility: Proctos kliniek
state: Utrecht
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer ziekenhuis
state: Zuid-Holland
city: Almere
country: Netherlands
facility: Flevoziekenhuis
city: Amsterdam
country: Netherlands
facility: University Medical Center location AMC
city: Capelle Aan Den IJssel
country: Netherlands
facility: IJsselland ziekenhuis
city: Utrecht
country: Netherlands
facility: Diakonessenhuis
Study officials:
References:
citation: van Oostendorp JY, Dekker L, van Dieren S, Bemelman WA, Han-Geurts IJM. Antibiotic Treatment foLlowing surgical drAinage of perianal abScess (ATLAS): protocol for a multicentre, double-blind, placebo-controlled, randomised trial. BMJ Open. 2022 Nov 8;12(11):e067970. doi: 10.1136/bmjopen-2022-067970.