Antibiotics as an Adjuvant in Patients With Acute Severe Ulcerative Colitis (AAASUC)

Post Graduate Institute of Medical Education and Research, Chandigarh

Status and phase

Completed

Phase 2

Conditions

Ulcerative Colitis

Inflammatory Bowel Diseases

Acute Severe Colitis

Treatments

Drug: Metronidazole

Other: Placebo infusion

Drug: Ceftriaxone

Study type

Interventional

Funder types

Other

Identifiers

NCT03794765

NK/5147/DM

Details and patient eligibility

About

The study is planned as a randomised control trial to study the adjuvant use of antibiotics (ceftriaxone and metronidazole) to achieve a clinical response in hospitalised patients with acute severe ulcerative colitis

Full description

All patients with active ulcerative colitis who present to the Outpatient department or the emergency services of PGIMER shall be screened. Those patients who have acute severe ulcerative colitis shall be assessed for inclusion into the study. Patients who fulfil the eligibility criteria will be randomised into two groups.

Group A will include patients in the intervention arm. They will be given intravenous antibiotics for three days. Injection ceftriaxone 1 gm will be prepared by reconstitution of the crystallized powder form in 100 ml of normal saline. This preparation will then be infused slowly over thirty minutes, after intradermal testing for hypersensitivity. Inj ceftriaxone 1gm IV will be given twelve hourly. Injection metronidazole 500 mg is available from pharmacies in solutions of 100 ml. It will be infused slowly over thirty minutes, three times per day, after intradermal testing for hypersensitivity. Both the drugs will be given for five days. In addition, they will receive the standard of care mentioned below.

Group B will include patients from the placebo arm. They will be given the standard of care as mentioned below. In addition, they will be infused 0.9 % saline of similar quantity, colour, and from similarly shaped bottles, for three days after sensitivity testing with the saline.

Detailed history and examination shall be done for all the patients. History regarding the stool output, any systemic symptoms, prior treatment history and history regarding any precipitant for the acute episode shall be taken. Examination will include vitals (pulse rate, blood pressure, temperature), general physical examination as well as an abdominal examination. All patients will undergo blood investigations on all three days. This includes a complete blood counts, kidney function tests, serum electrolytes, albumin, C-reactive protein, osteopontin, blood culture. Stool routine microscopic examination, fecal calprotectin, stool assay for clostridium difficile toxin will be done. X ray abdomen will be done on all three days to monitor the diameter of transverse colon. Patients will undergo an unprepared sigmoidoscopy with minimal air insufflation and mucosal biopsy. Biopsies will be taken for histological examination. Procalcitonin, fecal calprotectin and CRP shall be repeated on day 3 of admission.

All patients will be prescribed the standard treatment for acute severe colitis, which includes intravenous steroids (Inj Hydrocortisone 100 mg IV QID or Inj Methyprednisolone 60 mg iv OD), anticoagulation, (Inj Unfractionated heparin 5000 IU S/C BD), intravenous fluid supplementation and correction of electrolytes. Patients will be allowed orally and will be prescribed a diet of 25-30 kcal /kg/day.

Enrollment

50 patients

Sex

All

Ages

13+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Acute severe ulcerative colitis as described in European Crohn's and Colitis Organisation (ECCO) guidelines (adapted from Truelove and Witts)

Exclusion criteria

Patients who deny consent
Age<=12 years
Pregnant or lactating women
Severe uncontrolled comorbidities like diabetes mellitus, hypertension, coronary artery disease, chronic liver disease, chronic kidney disease, etc
History of antibiotic use in the past one month, excluding those who may have received a single dose of antibiotic in past 24 hrs
History of hypersensitivity or contraindication to steroids or the test drugs
Presence of toxic megacolon as defined by transverse colon diameter more than 5.5cm on abdominal X-ray
Patients with evidence of sepsis or active infection

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

50 participants in 2 patient groups, including a placebo group

Antibiotic

Experimental group

Description:

Standard of Care (steroids, prophylactic anticoagulation, oral nutrition) And Antibiotics (Inj Ceftriaxone 1 gram intravenous twice daily And Inj Metronidazole 500 mg intravenous thrice daily) for initial 48 hours

Treatment:

Drug: Ceftriaxone

Drug: Metronidazole

Placebo

Placebo Comparator group

Description:

Standard of care (steroids, prophylactic anticoagulation, oral nutrition) And Placebo infusions similar to the active drugs

Treatment:

Other: Placebo infusion