E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe chronic liver failure |
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E.1.1.1 | Medical condition in easily understood language |
Severe chronic liver failure |
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E.1.1.2 | Therapeutic area | Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09] |
MedDRA Classification |
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 find which of the following factors that predict albumin synthesis rate in patients with chronic liver failure: Child-Pugh score, MELD score, individual components of these two scores, respectively, indices of inflammation (P-ferritin, P-CRP), indices portal hypertension (splenomegaly, esophageal varices, platelet count), indices of coagulation (tromboelastometri), lactate clearance or dietary assessment. |
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E.2.2 | Secondary objectives of the trial |
• To characterize how the above mentioned factors and albumin synthesis rate correlate to capillary leakage measured by transcapillary escape rate of albumin.
• To characterize how do these same factors correlate to fibrinogen synthesis.
• To improve the prediction of impaired albumin synthesis rate by multiple linear regression.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients referred to Center for Digestive Diseases at Karolinska University Hospital Huddinge, as Child-Pugh B or C, for assessment of suitability for liver transplantation. At least 10 patients with Child-Pugh C will be included.
• Males and females ≥ 40 years
• Written informed consent
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E.4 | Principal exclusion criteria |
• Patients assessed for liver transplantation but with less severe liver failure, referred as Child-Pugh A
• Pregnancy or breast feeding patients
• Allergy to the investigational medical product
• Participation in other studies involving radiation or the use of stable isotopes within 30 days
• Paracentesis or gastrointestinal bleeding the last 7 days
• Other circumstance that makes the investigator judge patient participation unsuitable
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E.5 End points |
E.5.1 | Primary end point(s) |
Albumin synthesis rate (fractional and absolute, respectively) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Blood sampling for 90 min on study day |
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E.5.2 | Secondary end point(s) |
Child-Pugh score and MELD score, and components thereof, respectively, P-albumin, plasma volume, Transcapillary escape rate of albumin, fibrinogen synthesis rate, lactate clearance, P-fibrinogen, P-CRP, P-ferritin, blood platelet count, dietary assessment, nutrition status, splenomegaly, esophageal varices, and components of tromboelastometri. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Albumin and fibrinogen parameters and lactate clearance during the same 90 min the study day as the primary endpoint. All other parameters as close in time as pragmatically possible. |
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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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
This is an explorative study of human physiology in severe liver failure, how different indices of disease correlate to the impaired ability of the liver to synthesize albumin.
Tracer studies have no medical effects, but are used for studying human physiology. In this case, the IMP is used to measure plasma volume that is necessary to calculate absolute synthesis rate (mg/kg body weight/day) from fractional synthesis rate (% of plasma pool/day).
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
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 | No |
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
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The study is completed when we have collected data from 30 evaluable patients. At least 10 of these shall be classified as Child-Pugh C. |
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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 | 1 |
E.8.9.1 | In the Member State concerned days | |