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

Use of Antibiotics as an Adjuvant in Patients With Acute Severe Ulcerative Colitis: A Randomised Trial

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

Study Overview

• Status: Completed
• Conditions: Inflammatory Bowel Diseases; Ulcerative Colitis; Acute Severe Colitis
• Intervention / Treatment: Drug: Ceftriaxone; Drug: Metronidazole; Other: Placebo infusion

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• India
  • Chandigarh, India, 160012
    • Postgraduate Institute of Medical Education and Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 11 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Antibiotic; 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	Drug: Ceftriaxone; Injection ceftriaxone 1 gm will be prepared by reconstitution of the crystallised 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.; Drug: Metronidazole; 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
Placebo Comparator: Placebo; Standard of care (steroids, prophylactic anticoagulation, oral nutrition) And Placebo infusions similar to the active drugs	Other: Placebo infusion; Similar placebo infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response as defined by the Oxford's criteria	Patients will be defined as complete responders, partial responders or non-responders	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion needing second line therapy	Second line therapy : Intravenous Infliximab, Intravenous cyclosporine or others	28 days
Proportion needing colectomy	Number of patients in each group needing colectomy	28 days
Mortality	Number of patients in having mortality	28 days
Duration of hospital stay	Length of hospital stay in each group	28 days
Change in serum CRP levels		48 hours
Change in Mayo disease severity index		48 hours
Patients with Reduction in fecal calprotectin by >100 mcg/mg	Number of patients in each group having the predefined decline in fecal calprotectin	48 hours

Collaborators and Investigators

• Sponsor: Postgraduate Institute of Medical Education and Research
• Investigators: Principal Investigator: Vishal Sharma, Postgraduate Institute of Medical Education and Research; Principal Investigator: Shubhra Mishra, Postgraduate Institute of Medical Education and Research

Publications and helpful links

General Publications

• Mishra S, Mandavdhare HS, Singh H, Choudhury A, Shah J, Ram S, Kalsi D, Samanta J, Prasad KK, Sharma AK, Dutta U, Sharma V. Adjuvant use of combination of antibiotics in acute severe ulcerative colitis: A placebo controlled randomized trial. Expert Rev Anti Infect Ther. 2021 Jul;19(7):949-955. doi: 10.1080/14787210.2021.1856656. Epub 2020 Dec 14.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Actual): March 4, 2020
• Study Completion (Actual): April 4, 2020

Study Registration Dates

• First Submitted: January 4, 2019
• First Submitted That Met QC Criteria: January 4, 2019
• First Posted (Actual): January 7, 2019

Study Record Updates

• Last Update Posted (Actual): December 11, 2020
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Metronidazole; Antibiotics; Ceftriaxone
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Ulcer; Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Metronidazole; Ceftriaxone
• Other Study ID Numbers: NK/5147/DM

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No