Antibiotics as an Adjuvant in Patients With Acute Severe Ulcerative Colitis

NCT ID: NCT03794765

Last Updated: 2020-12-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-04-01

Study Completion Date

2020-04-04

Brief Summary

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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

Detailed Description

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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.

Conditions

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Ulcerative Colitis Inflammatory Bowel Diseases Acute Severe Colitis

Keywords

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Antibiotics Ceftriaxone Metronidazole

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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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

Group Type EXPERIMENTAL

Ceftriaxone

Intervention Type DRUG

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.

Metronidazole

Intervention Type DRUG

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

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

Group Type PLACEBO_COMPARATOR

Placebo infusion

Intervention Type OTHER

Similar placebo infusion

Interventions

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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.

Intervention Type 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

Intervention Type DRUG

Placebo infusion

Similar placebo infusion

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

13 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Post Graduate Institute of Medical Education and Research, Chandigarh

OTHER

Sponsor Role lead

Responsible Party

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Vishal Sharma

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Vishal Sharma

Role: PRINCIPAL_INVESTIGATOR

Post Graduate Institute of Medical Education and Research, Chandigarh

Shubhra Mishra

Role: PRINCIPAL_INVESTIGATOR

Post Graduate Institute of Medical Education and Research, Chandigarh

Locations

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Postgraduate Institute of Medical Education and Research

Chandigarh, , India

Site Status

Countries

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India

References

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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.

Reference Type RESULT
PMID: 33245002 (View on PubMed)

Other Identifiers

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NK/5147/DM

Identifier Type: -

Identifier Source: org_study_id