Alcoholic HepatitisEarly Phase 1NCT02326103
Randomised Open-label Multicenter Study Evaluating Ciprofloxacin in Severe Alcoholic Hepatitis
A Early Phase 1 study testing Ciprofloxacin in people with Alcoholic Hepatitis and Alcoholic Cirrhosis, run by University of Helsinki at 1 site in Finland.
Trial summary
The study is aimed to evaluate the additional role of ciprofloxacin therapy in severe alcoholic hepatitis combined to prednisolone therapy in an open-label placebo controlled manner. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Alcoholic Hepatitis, Alcoholic Cirrhosis
- What is being tested?
- Ciprofloxacin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteFinland
- Study dates
- Apr 2015to Jan 2017
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Severe alcoholic hepatitis; Maddrey above 300
Who cannot join
- Viral hepatitis Remarkable bleeding in the gastrointestinal tract Serious bacterial infection Hepatorenal syndrome Earlier participation in this study Malignant disease not in remission Other liver disease affecting remarkably the outcome of alcoholic liver disease Mental retardation
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomised Open-label Multicenter Study Evaluating Ciprofloxacin in Severe Alcoholic Hepatitis in Addition to Prednisolon Therapy
The study is aimed to evaluate the additional role of ciprofloxacin therapy in severe alcoholic hepatitis combined to prednisolone therapy in an open-label placebo controlled manner.
Read the detailed description
Introduction: Alcoholic hepatitis (AH) is an inflammatory liver injury associated with longstanding excess alcohol consumption. Disease spectrum varies from asymptomatic transaminase elevations to fulminate liver failure. In hospital mortality in patients with severe alcoholic hepatitis not responding to corticosteroids is over 30 %.
Alcohol increases gut permeability and promotes the translocation of lipopolysaccharide (LPS) from the gut lumen the portal vein, and further to Kupffer cells, where LPS binds to CD14, ultimately activating multiple cytokine genes.
Diagnosis of AH is based on history of heavy alcohol use, symptoms like jaundice and on typical laboratory findings, and in uncertain cases on liver biopsy.
Determination of the severity of alcoholic hepatitis is essential for assessment of the disease prognosis and selection therapy. Cessation of alcohol consumption is mandatory for further therapy. Several scoring systems are available to assess the severity and the prognosis of alcohol hepatitis. Maddrey discrimination function (DF) is most widely used and enables to identify patients with severe alcohol hepatitis responding to corticosteroid therapy.
The first line therapy in severe alcoholic hepatitis (DF≥32) is prednisolone. However, those not responding to steroids have 77 % 6 months mortality.
New treatment options for severe AH are desperately needed. Although increased bacterial and LPS translocation are considered to have central role in the pathogenesis of AH no controlled studies of antibiotics in alcoholic hepatitis has been published. In Finland 600 AH requiring hospitalization are diagnosed annually.
Study objective: To evaluate to additional role of ciprofloxacin therapy in severe alcoholic hepatitis combined to prednisolone therapy.
Moreover, we try to find new and better predictors for liver injury and treatment response.
Patients: 150 AH patients, with Maddrey DF >32.
Randomization: Patients with severe AH are randomized at hospitalization 1:1 to receive:
- Prednisolone 40 mg/day for 1 month, with decreasing by 5 mg/week + ciprofloxacin 1000 mg/ day for 120 days or
- Prednisolone 40 mg/day for 1 month, with decreasing by 5 mg/week + placebo/ day for 120 days Measurement of response Early change in bilirubin levels (ECBL= S-Bil(Day 0)-S-Bil(Day7 )>0 Lille Score >0.45 day 7. Change in serum sterol levels as surrogate markers of cholesterol synthesis (reflecting liver function and severity of cholestasis) Primary end point Mortality at day 28, at 6 months and at 12 months Secondary end points: Proportion of patients with early change in bilirubin levels (ECBL= S-Bil(Day 0)-S-Bil(Day7 )>0 Proportion of patients with Lille Score >0.45 day 7 Recovery of liver function parameters in 1 and 3 months
- Conditions
- Alcoholic Hepatitis, Alcoholic Cirrhosis
- Being tested
- Ciprofloxacin, Placebo
- Keywords
- alcoholic, hepatitis, cirrhosis, cholesterol metabolites, ciprofloxacin
- Medical subject headings
- Hepatitis, Alcoholic, Liver Cirrhosis, Alcoholic, Hepatitis, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CiprofloxacinDrug
Comparison of ciprofloxacin with placebo in alcoholic hepatitis
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Ciprofloxacin | Active comparator | Oral administration of Ciprofloxacin 500mg twice daily Receives: Drug: Ciprofloxacin |
| Placebo | Placebo comparator | Oral administration of Placebo pill twice daily Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Death at 28 days
Measured: 28 days after randomisation
Death at 3 months
Measured: 3 months after randomisation
Death at 6 months
Measured: 6 months after randomisation
Secondary outcomes (2)
Early reduction in serum bilirubin level
Measured: 7 days after randomisation
Surrogate markers of liver function
Improvement of surrogate markers of cholesterol synthesis and liver synthesis capacity, e.g., lathosterol, cholestenol and desmosterol
Measured: 7 days to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Dec 2014 (estimated)
- Study startApr 2015
- Primary completionJan 2017
- Study completionJan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alcoholic HepatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Helsinki
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Markku Nissinen, University of Helsinki
- Investigators
- Perttu Sahlman, MD, Principal investigator, University Hospital of Helsinki
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02326103
- Sponsor's protocol ID
- HELSINKIU
- Status last verified
- Jan 2017
- First submitted
- 22 Dec 2014
- Last updated
- 19 Jan 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No: No IPD will be shared with other researchers during the study or during the analysis of the results.
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised Open-label Multicenter Study Evaluating Ciprofloxacin in Severe Alcoholic Hepatitis in Addition to Prednisolon Therapy
- ClinicalTrials.gov ID
- NCT02326103
- Acronym / sponsor ID
- HELSINKIU
- Conditions
- Alcoholic Hepatitis, Alcoholic Cirrhosis
- Keywords
- alcoholic, hepatitis, cirrhosis, cholesterol metabolites, ciprofloxacin
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- University of HelsinkiUniversity, hospital or other
- Study start
- Apr 2015
- Primary completion
- Jan 2017 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 25 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is aimed to evaluate the additional role of ciprofloxacin therapy in severe alcoholic hepatitis combined to prednisolone therapy in an open-label placebo controlled manner.
Detailed description
Introduction: Alcoholic hepatitis (AH) is an inflammatory liver injury associated with longstanding excess alcohol consumption. Disease spectrum varies from asymptomatic transaminase elevations to fulminate liver failure. In hospital mortality in patients with severe alcoholic hepatitis not responding to corticosteroids is over 30 %.
Alcohol increases gut permeability and promotes the translocation of lipopolysaccharide (LPS) from the gut lumen the portal vein, and further to Kupffer cells, where LPS binds to CD14, ultimately activating multiple cytokine genes.
Diagnosis of AH is based on history of heavy alcohol use, symptoms like jaundice and on typical laboratory findings, and in uncertain cases on liver biopsy.
Determination of the severity of alcoholic hepatitis is essential for assessment of the disease prognosis and selection therapy. Cessation of alcohol consumption is mandatory for further therapy. Several scoring systems are available to assess the severity and the prognosis of alcohol hepatitis. Maddrey discrimination function (DF) is most widely used and enables to identify patients with severe alcohol hepatitis responding to corticosteroid therapy.
The first line therapy in severe alcoholic hepatitis (DF≥32) is prednisolone. However, those not responding to steroids have 77 % 6 months mortality.
New treatment options for severe AH are desperately needed. Although increased bacterial and LPS translocation are considered to have central role in the pathogenesis of AH no controlled studies of antibiotics in alcoholic hepatitis has been published. In Finland 600 AH requiring hospitalization are diagnosed annually.
Study objective: To evaluate to additional role of ciprofloxacin therapy in severe alcoholic hepatitis combined to prednisolone therapy.
Moreover, we try to find new and better predictors for liver injury and treatment response.
Patients: 150 AH patients, with Maddrey DF >32.
Randomization: Patients with severe AH are randomized at hospitalization 1:1 to receive:
- Prednisolone 40 mg/day for 1 month, with decreasing by 5 mg/week + ciprofloxacin 1000 mg/ day for 120 days or
- Prednisolone 40 mg/day for 1 month, with decreasing by 5 mg/week + placebo/ day for 120 days Measurement of response Early change in bilirubin levels (ECBL= S-Bil(Day 0)-S-Bil(Day7 )>0 Lille Score >0.45 day 7. Change in serum sterol levels as surrogate markers of cholesterol synthesis (reflecting liver function and severity of cholestasis) Primary end point Mortality at day 28, at 6 months and at 12 months Secondary end points: Proportion of patients with early change in bilirubin levels (ECBL= S-Bil(Day 0)-S-Bil(Day7 )>0 Proportion of patients with Lille Score >0.45 day 7 Recovery of liver function parameters in 1 and 3 months
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ciprofloxacin | Active comparator | Drug: CiprofloxacinOral administration of Ciprofloxacin 500mg twice daily |
| Placebo | Placebo comparator | Drug: PlaceboOral administration of Placebo pill twice daily |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Severe alcoholic hepatitis; Maddrey above 300
Key exclusion criteria (1 listed)
- Viral hepatitis Remarkable bleeding in the gastrointestinal tract Serious bacterial infection Hepatorenal syndrome Earlier participation in this study Malignant disease not in remission Other liver disease affecting remarkably the outcome of alcoholic liver disease Mental retardation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CiprofloxacinComparison of ciprofloxacin with placebo in alcoholic hepatitis | Drug | Ciprofloxacin |
| Placebo | Drug | Placebo |
Primary outcome
Death at 28 days
Time frame: 28 days after randomisation
Death at 3 months
Time frame: 3 months after randomisation
Death at 6 months
Time frame: 6 months after randomisation
2 secondary outcomes
Early reduction in serum bilirubin level
Time frame: 7 days after randomisation
Surrogate markers of liver function
Time frame: 7 days to 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2017.
- Individual participant dataSharing planned: No. No IPD will be shared with other researchers during the study or during the analysis of the results.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Perttu Sahlman, MD principal investigator
University Hospital of Helsinki
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Ciprofloxacin in people with Alcoholic Hepatitis and Alcoholic Cirrhosis, run by University of Helsinki at 1 site in Finland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Death at 28 days (time frame: 28 days after randomisation). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2017; AzTrials last refreshed its copy on 3 Nov 2026.