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

Sponsor

Postgraduate Institute of Medical Education and Research (Other)

Overall Status

Completed

CT.gov ID

NCT03794765

Collaborator

(none)

Enrollment

Location

Arms

12.1

Actual Duration (Months)

4.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Ulcerative Colitis Inflammatory Bowel Diseases Acute Severe Colitis	Drug: Ceftriaxone Drug: Metronidazole Other: Placebo infusion	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 1, 2019

Actual Primary Completion Date :

Mar 4, 2020

Actual Study Completion Date :

Apr 4, 2020

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Clinical response as defined by the Oxford's criteria [48 hours]
Patients will be defined as complete responders, partial responders or non-responders

Secondary Outcome Measures

Proportion needing second line therapy [28 days]
Second line therapy : Intravenous Infliximab, Intravenous cyclosporine or others
Proportion needing colectomy [28 days]
Number of patients in each group needing colectomy
Mortality [28 days]
Number of patients in having mortality
Duration of hospital stay [28 days]
Length of hospital stay in each group
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 [48 hours]
Number of patients in each group having the predefined decline in fecal calprotectin

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Postgraduate Institute of Medical Education and Research	Chandigarh		India	160012

Sponsors and Collaborators

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