E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Alcoholic Hepatitis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10019805 |
E.1.2 | Term | Hepatobiliary disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate whether Sulfasalazine (an inhibitor of NFkappaB activation and hepatic stellate cell activation in vitro and in vivo) is an effective human anti-fibrotic agent in the treatment of accelerated liver fibrosis associated with acute alcoholic hepatitis. |
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E.2.2 | Secondary objectives of the trial |
To evaluate whether Sulfasalazine treatment reduces the development of cirrhosis and in time the morbidity and mortality from alcoholic hepatitis. The effects of treatment on specific molecular markers of liver fibrosis, namely collagen type I, alpha smooth muscle actin, tissue inhibitors of metalloproteinases and other mediators will also be analyzed. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All patients will have a diagnosis of acute alcoholic hepatitis based on clinical findings, history of alcohol consumption of >80g/day for men and 60g/day for women and liver histology. Other causes of liver disease will be excluded by standard investigations. The diagnosis of alcoholic hepatitis will be confirmed by liver biopsy prior to trial entry. |
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E.4 | Principal exclusion criteria |
Informed consent refused by patient. Clearly moribund patients or patients with evidence of established irreversible triple organ failure in whom survival is extremely unlikely. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Matched liver fibrosis scores pre- and post-treatment. Biopsies will be blinded and assessed by two independent expert liver histopathologists. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
It is not envisaged that the situation will arise where the trial will have to be stopped as Sulfasalazine has a long and established track record. Should any situation arise in which this assumption is called into doubt we will suspend the study and seek further guidance from the ethics commitee. With this in mind we have asked Dr Matthew Cramp to serve as a completely independent adjudicator of any suspected adverse events or complications. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |