E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Sepsis with Renal Failure |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040050 |
E.1.2 | Term | Sepsis NOS |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038435 |
E.1.2 | Term | Renal failure |
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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 |
Confirmation of previous trial data on safety and efficacy outcome in septic patients with renal failure: • • To investigate the effect of AP on renal function and associated clinical parameters in sepsis patients with renal failure. • To investigate the safety and tolerability of AP in sepsis patients with renal failure • To investigate the pharmacokinetics of AP in sepsis patients with renal failure • To investigate the effect of AP on inflammatory parameters in sepsis patients with renal failure
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients ≥18 years and ≤80 years. • Proven or suspected infection. • Two out of four SIRS criteria of systemic inflammation, as follows: • Core temperature ≥38° or ≤36° Celsius. • Heart rate ≥90 beats/min (unless the patient has a medical condition known to increase heart rate or is receiving treatment that would prevent tachycardia). • Respiratory rate ≥20 breaths/min, a PaCO2 ≤32mmHg or the use of mechanical ventilation for an acute respiratory process. • White-cell count ≥12,000/mm3 or ≤4,000/mm3 or a differential count showing >10 percent immature neutrophils. • Acute renal failure, defined as - rise in serum creatinine level to ≥150μmol/L within the previous 48 hours, in the absence of primary underlying renal disease OR - Minimally a stage 1 Kidney Injury according to AKIN criteria: Increase in serum creatinine ≥26.2 µmol/l (0.3mg/dl) or increase to ≥150% (≥1.5 -fold) from baseline in the previous 48 hours in the absence of primary underlying renal disease and where baseline creatinine is less than 150umol/l OR - minimally a stage 1 Kidney injury according to AKIN Urine Output criteria: Urine Output of ≤ 0.5mg/kg/h for ≥6 h and following adequate fluid resuscitation when applicable, in the absence of underlying primary renal disease and where baseline creatinine is less than 150umol/l • Written informed consent obtained prior to any study intervention.
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E.4 | Principal exclusion criteria |
• • Pregnant women or nursing mothers and fecund females who are not on effective contraception (chemical: pill; or mechanical: IUD) • Known HIV (sero-positive) patients • Patients already on dialysis (RRT) at entry • Patients receiving immunosuppressant therapy or on chronic high doses of steroids equivalent to prednisone 1mg/Kg/day • Patients expected to have rapidly fatal disease within 24 hours • Known confirmed gram-positive sepsis • Known confirmed fungal sepsis • Acute pancreatitis with no established source of infection • Patients not expected to survive for 28 days due to other medical conditions such as end-stage neoplasm or other diseases • Participation in another investigational study within 90 days prior to start of the study which might interfere with this study • Any previous administration of active study medication. • Known allergy for dairy (bovine) products including cow milk. • Sepsis without renal failure as defined in the Entry Criteria. • History of chronic renal failure or history of persistent creatinine level equal or greater than 150umol/L prior to entry for reasons other than the current sepsis condition".
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E.5 End points |
E.5.1 | Primary end point(s) |
Criteria for Evaluation of Safety • Adverse events • ECG variables • Biochemical safety variables • Hematological variables • Coagulation variables • Serial serum creatinine • Urea / Blood Urea Nitrogen (BUN) • Requirement of Renal Replacement Therapy (RRT) • Duration of RRT • Creatinine clearance • Urinary protein excretion
Primary efficacy variables for evaluation of the effect on renal function: • Serum creatinine • Creatinine clearance • Requirement for RRT
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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 | 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial months | 11 |