E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hepatorenal Syndrome Type 1 |
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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 | LLT |
E.1.2 | Classification code | 10019846 |
E.1.2 | Term | Hepatorenal syndrome |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
to demonstrate that intravenous terlipressin is safe and effective in the treatment of patients with hepatorenal syndrome (HRS) type 1 when compared to placebo with regard to treatment success at 14 days, i.e., survival with a reversal of HRS to serum creatinine values at or below 1.5 mg/dL |
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E.2.2 | Secondary objectives of the trial |
to demonstrate that terlipressin improves renal function and survival compared to placebo |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provide written informed consent by patient or legal representative before initiation of any study related procedures. 2. At least 18 years old 3. Chronic liver disease. 4. Acute liver disease, i.e. de novo onset within 6 weeks; e.g. viral and/or alcoholic hepatitis (see also exclusion criteria 6). 5.Rapidly progressive reduction in of renal function, e.g. doubling of serum creatinine to >2.5mg/dL in less than 2 weeks prior to HRS diagnosis, or a 50% reduction of the initial 24 hour creatinine clearance to a level lower than 20 mL/min. 6. Low GFR, as indicated by serum creatinine >1.5 mg/dL, or 24 h creatinine clearance of <40mL/min 7. No sustained improvement in renal function (decrease of serum creatinine to 1.5mg/dL or less or increase in creatinine clearance to 40mL/min or more) after diuretic withdrawal and plasma volume expansion with 1.5 L isotonic saline. 8. Proteinuria lower than 500 mg/dL per day 9. No evidence of granular casts on urinalysis 10. No ultrasonographic evidence of obstructive uropathy or parenchymal renal disease
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E.4 | Principal exclusion criteria |
1. Ongoing Shock 2. Uncontrolled (ongoing) bacterial infection 3. Current fluid losses, i.e. GI fluid losses (repeat vomiting or intense diarrhea) or renal fluid losses (eg weight loss >500g/d for several days in patients with ascites without peripheral edema or 1000 g/d in patients with peripheral edema) 4. Current or recent treatment with nephrotoxic drugs, eg aminoglycosides, NSAIDs within 4 weeks 5. Estimated life expectancy of less than 3 days 6. Acute liver disease due to factors known to be also directly nephrotoxic (e.g. acetaminophen overdose, mushroom [Amanita] poisoning) 7. Confirmed pregnancy 8. Severe cardiovascular disease as judged by investigator 9. Evidence of intrinsic or parenchymal renal disease (eg acute tubular necrosis) 10. Known allergy to terlipressin, or known sensitivity to any component of the products 11 Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of randomization.
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of treatment success at day 14, defined as the percentage of patients alive with reversal of HRS (serum creatinine at or below 1.5 mg/dL, with at least 2 measurements 48 ± 2h apart), without dialysis or recurrance of HRS. |
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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The active study period extends from the time of study drug administration through Day 14. The follow-up period begins after the end of the active study period and ends 180 days after start of study drug. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |