Cirrhosis Clinical Trial
Official title:
COMPARATIVE STUDY OF NORFLOXACIN AND PROBIOTICS ON PORTAL PRESSURE IN PATIENTS WITH CIRRHOSIS AND LARGE VARICES WHO HAVE NEVER BLED IN THE PAST
NCT number | NCT01134692 |
Other study ID # | NG002 |
Secondary ID | |
Status | Recruiting |
Phase | Phase 3 |
First received | June 1, 2010 |
Last updated | June 1, 2010 |
Chronic peripheral and splanchnic vasodilatation are the hallmark hemodynamic abnormality in
cirrhosis and contribute to the pathogenesis of portal hypertension.
Alterations in intestinal motility and bacterial overgrowth in gut may predispose to the
development of bacteraemia and endotoxaemia in cirrhotic patients which play a role in the
hyperdynamic circulatory syndrome of cirrhosis. Probiotic therapy is aimed at changing the
make-up of the indigenous microflora by administering specific strains of non-pathogenic and
potentially beneficial microflora. In this study, the investigators hypothesize that a
modification in the composition of the endogenous digestive microflora by oral
bacteriotherapy with high potency probiotic preparations could be a safe way to regulate the
portal pressure.
As there is a relative paucity in effective pharmacological treatment for portal
hypertension, these novel and innovative therapy might provide important alternative or
adjunct therapy to beta blockers in the clinical management of patients with portal
hypertension.
Aims and objectives
To study in patients with cirrhosis and large varices whether probiotics and/or norfloxacin
given for 2 months :
1. achieve a reduction in HVPG
2. alter the endotoxin and cytokine levels, and improve systemic inflammatory responses
3. well tolerated.
Inclusion criteria:
Consecutive patients of cirrhosis with portal hypertension who fulfill the following
criteria:
1. Diagnosed cases of cirrhosis (by clinical, biochemical and radiological criteria with
or without liver biopsy)
2. No history of upper GI bleeding in the past
3. Endoscopically documented large esophageal varices
Exclusion criteria
1. history of gastrointestinal bleeding
2. patients who have received beta blockers for portal hypertension in the past 6 weeks.
3. hepatic encephalopathy
4. ongoing bacterial infection,
5. Spontaneous bacterial peritonitis
6. active alcoholism or illicit drug abuse
7. alcoholic hepatitis
8. Treatment with antibiotics in the preceding 2 weeks.
9. presence of hepatocellular carcinoma,
10. portal vein thrombosis
11. serum creatinine>1.5 mg/dL,
12. treatment with vasoactive drugs in the past 6 weeks,
13. history of arterial hypertension, congestive heart failure or arterial occlusive
disease, and
14. Refusal to participate.
15. Active smokers.
Study plan:
Ethical approval will be obtained prior to study initiation. Patients presenting to
Department of Gastroenterology, GB Pant Hospital will be recruited in the study. Patients
will be evaluated regarding the eligibility for the study. After being found eligible for
the study, if the patient agrees to participate in the study, a signed informed consent will
be obtained. Baseline HVPG will be measured in all patients and then they will be randomized
into 3 groups:.
1. Group 1: Beta blockers + placebo
2. Group 2: Beta blockers + Norfloxacin (400mg BD)
3. Group 3: Beta blockers + probiotics. (one sachet of VSL#3 BD)
30 patients will be enrolled into each group. The treatment will be continued for 2 months.
The study design is a randomized double-blinded placebo controlled trial.
Once patients have been enrolled, they will undergo baseline investigations. Blood will be
drawn from both peripheral and hepatic veins and sent for routine parameters,
pro-inflammatory cytokines (IL-1b, IL-6, IL-10, TNF-α, endotoxins, NO2 and NO3 levels, PRA,
BNP). Samples will be stored at -70 ºC. Baseline vitals will be recorded.
Patients will be called at the end of 1 month for assessment of compliance and then at the
end of the study (2 months) to repeat the HVPG and the same parameters as at the time of
enrollment
End Points:
1. Primary
a. Change in HVPG levels as compared with baseline, to define responder (≥20% reduction
in HVPG or ≤ 12 mm Hg).
2. Secondary
1. Change in digestive flora
2. Reduction in serum and hepatic endotoxin and cytokine levels
3. Assessment of improvement in the renal parameters and Systemic inflammatory
response syndrome
4. Improvement in the markers of oxidative injury
5. Adverse effects
Status | Recruiting |
Enrollment | 0 |
Est. completion date | |
Est. primary completion date | |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 12 Years to 75 Years |
Eligibility |
Inclusion Criteria: Consecutive patients of cirrhosis with portal hypertension who fulfill the following criteria: 1. Diagnosed cases of cirrhosis (by clinical, biochemical and radiological criteria with or without liver biopsy) 2. No history of upper GI bleeding in the past 3. Endoscopically documented large esophageal varices Exclusion Criteria: 1. history of gastrointestinal bleeding 2. patients who have received beta blockers for portal hypertension in the past 6 weeks. 3. hepatic encephalopathy 4. ongoing bacterial infection, 5. Spontaneous bacterial peritonitis 6. active alcoholism or illicit drug abuse 7. alcoholic hepatitis 8. Treatment with antibiotics in the preceding 2 weeks. 9. presence of hepatocellular carcinoma, 10. portal vein thrombosis 11. serum creatinine>1.5 mg/dL, 12. treatment with vasoactive drugs in the past 6 weeks, 13. history of arterial hypertension, congestive heart failure or arterial occlusive disease, and 14. Refusal to participate. 15. Active smokers. |
Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Prevention
Country | Name | City | State |
---|---|---|---|
India | GB Pant hospital | Delhi |
Lead Sponsor | Collaborator |
---|---|
Govind Ballabh Pant Hospital |
India,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change in HVPG levels as compared with baseline, to define responder (=20% reduction in HVPG or = 12 mm Hg). | 2 months | No | |
Secondary | Assessment of improvement in the renal parameters and Systemic inflammatory response syndrome | 2 months | No | |
Secondary | Adverse effects | 2 months | Yes |
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