| CTRI Number |
CTRI/2023/12/060803 [Registered on: 27/12/2023] Trial Registered Prospectively |
| Last Modified On: |
29/01/2024 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
To study the efficacy of Rifaximin (drug) vs Norfloxacin (drug) in liver disease |
|
Scientific Title of Study
|
Efficacy of Rifaximin vs Norfloxacin for Secondary Prophylaxis of SBP (NORRIF Trial): A Randomized control trial. |
| Trial Acronym |
NORRIF |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| None |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Jayashree Biswas |
| Designation |
Senior Resident,Department of hepatology |
| Affiliation |
Institute of Liver and Biliary Sciences |
| Address |
Room No. 3330, Department of Hepatology, Phase II, 3rd Floor, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi-110070.
South West
DELHI
110070
India |
| Phone |
01146300000 |
| Fax |
|
| Email |
jayashreeb790@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Manoj Kumar Sharma |
| Designation |
Professor & Head, Department of Hepatology |
| Affiliation |
Institute of Liver and Biliary Sciences |
| Address |
Room No. 3330, Department of Hepatology, Phase II, 3rd Floor, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi-110070.
South West
DELHI
110070
India |
| Phone |
01146300000 |
| Fax |
|
| Email |
manojkumardm@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Manoj Kumar Sharma |
| Designation |
Professor & Head, Department of Hepatology |
| Affiliation |
Institute of Liver and Biliary Sciences |
| Address |
Room No. 3330, Department of Hepatology, Phase II, 3rd Floor, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi-110070.
DELHI
110070
India |
| Phone |
01146300000 |
| Fax |
|
| Email |
manojkumardm@gmail.com |
|
|
Source of Monetary or Material Support
|
| Institute of Liver & Biliary Sciences,D-1,Vasant Kunj,New Delhi-110070 |
|
|
Primary Sponsor
|
| Name |
Institute of Liver and Biliary Sciences |
| Address |
Room No. 3330, Department of Hepatology, Phase II, 3rd Floor, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi-110070.
|
| Type of Sponsor |
Research institution and hospital |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Jayashree Biswas |
Institute of Liver and Biliary Sciences |
Room No. 3330, Department of Hepatology, Phase II, 3rd Floor, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi-110070.
South West
DELHI |
01146300000
jayashreeb790@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee, Institute of Liver and Biliary Sciences |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: K769||Liver disease, unspecified, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Norfloxacin |
Norfloxacin 400 mg OD
Duration: 1 year
Route: Oral |
| Intervention |
Rifaximin |
Rifaximin 550 mg BD
Duration: 1 year
Route: Oral |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
1) Age>18 years
2) Cirrhosis (of any etiology) with ascites
3) Prior incident SBP |
|
| ExclusionCriteria |
| Details |
1. Allergy to norfloxacin or rifaximin
2. Recent history of upper gastrointestinal bleed (UGIB) within 2 weeks
3. Patients with a history of multiple episodes of SBP
4. Patients with inoperable or not treatable HCC or other non-hepatic malignancy
5. Patients on immunosuppression
6. HIV infected
7. Post liver transplant
8. Recent (<6 months) abdominal surgery
9. Pregnant/lactating women
10. Other causes of ascites like tubercular or malignancy
11. Patients developing SBP on Norfloxcacin |
|
|
Method of Generating Random Sequence
|
Permuted block randomization, fixed |
|
Method of Concealment
|
On-site computer system |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Incidence of recurrence of SBP within 6 months |
6 months |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Incidence of recurrence of SBP within12 months |
12 months |
| Incidence of other site infections within 6 and 12 months |
6 and 12 months |
| Incidence of other complications (HE, variceal bleed, Refractory ascites, AKI) within 6 and 12 months) |
6 and 12 months |
| Transplant free survival by 6 and 12 months |
6 and 12 months |
| Median change in CTP, MELD, MELD-Na scores by 6 months and 12 months |
6 months and 12 months |
| Changes in gut microbiome in both groups by 6 and 12 months |
6 months and 12 months |
| Side effects in both groups |
12 months |
| Resistance patterns of infections in each group |
12 months |
|
|
Target Sample Size
|
Total Sample Size="280"
Sample Size from India="280"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 2/ Phase 3 |
|
Date of First Enrollment (India)
|
08/01/2024 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="6"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Hypothesis:-Rifaximin will be more effective in decreasing the incidence of SBP in patients with cirrhosis and prior episode of SBP
AIM:-.To study the efficacy and safety of Rifaximin vs Norfloxacin in preventing incident SBP, preventing non-SBP infections, and improving transplant free survival in patients with cirrhosis and previous episode of SBP
Methodology Single centered Open labeled Randomized Controlled Trial
Randomization will be done by block randomization method taking block size as 10. Data will be entered in Microsoft Excel and will be analysed by SPSS Version 28.Categorical Data will be represented as frequency (%) and will be analysed using Chi square or Fisher Exact Test as appropriate.Continuous Data will be represented as Mean +/- SD and compared using Student T test or Mann Whitney as per normality conditions are met or not.Beside this an appropriate analysis like survival analysis will be carried out at the time of Data Analysis.P value <0.05 will be considered as significant.
Rescue therapy: To be given to patients who develop SBP while on secondary prophylaxis, these patients will initially be treated by iv medication in hospital settings followed by change in therapy. • Patients in Rifaximin limb developing SBP will switch to Norfloxacin • Patients in Norfloxacin limb developing SBP will switch to Rifaximin
Treatment Failure: Defined as development of SBP at end of 6 months or 1 year of treatment.
Study population: age >18 years with prior incident SBP
Study design: Randomised case controlled trial
Study period: 1year after ethical clearance
Sample size: 280 (140 in each arm)
Intervention: This RCT will be conducted at ILBS New Delhi Monitoring and assessment: Monitoring will be done forall the parameters of the objective. Documentation will be done for any adverse effects which will happen. STATISTICAL ANALYSIS: Assuming incidence of SBP over 6 months is 4% in Rifaximin & 15% in Norfloxacin Alpha 5% and power 80%. Enrollment of 260 cases (130 in each arm). Assuming dropout rate 10%.Total study cases calculated as 280 (140 in each arm). Random allocation in each arm by block method taking 10 as block size
|