E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053879 |
E.1.2 | Term | Sepsis syndrome |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 |
Stage 1 (i) What are the pharmacokinetics of 50mg and 20mg oral melatonin in patients with sepsis? (ii) Which dose is most suitable based on the pharmacokinetics in (i)? (iii) What is the most suitable dosing interval based on results from (i)?
Stage 2 (iv) What effect does oral melatonin have on the defined outcome measures compared to placebo? (v) What effects does melatonin have on mRNA expression under conditions of sepsis?
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Adult patients (16 y or above) on the ICU at Aberdeen Royal Infirmary with sepsis due to community acquired pneumonia who are within 24h of fulfilling the criteria for sepsis with clinical suspicion of pneumonia and the presence of chest X-ray changes consistent with pneumonia will be recruited. The criteria for sepsis are:
• clinical suspicion or evidence of acute infection • systemic inflammatory response syndrome, defined by two or more of the following: 1. Core temperature <36 or >38°C; 2. tachycardia: heart rate > 90 beats/min; 3. tachypnoea: respiratory rate > 20 breaths/min or ventilated; 4. leucocyte count >12 x 10^9/L or <4 x 10^9/L.
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E.4 | Principal exclusion criteria |
Exclusions: • <16 years old, • have a life expectancy <24h, • have metastatic cancer or immunosuppression, • are receiving steroids (>20mg/d prednisolone or equivalent, used regularly for >2 weeks prior to ICU admission) or are • women of child bearing potential without a negative pregnancy test or a history of surgical sterilization. • patients receiving fluvoxamine or nifedipine, • those with overt hepatic failure • those who are unable to understand or comply with the requirements of the trial
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E.5 End points |
E.5.1 | Primary end point(s) |
Stage 1. The primary endpoint for Stage 1 is administration of 2 oral melatonin doses with no adverse reactions and approval by the DMC of dose and dosing interval decisions for Stage 2.
Stage 2. Since this is a pilot study there is no primary outcome measure other than completion of the trial. we will be assessing a range of biomarkers and clinical measures for use as primary outcome measures in a subsequent properly powered trial. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Stage 1: 24 h after last subject Stage 2: 28 days after last subject randomised |
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 |
Determination of pharmacokinetics and dosing interval in patients |
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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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Stage 1 is open label, Stage 2 is randomised, double blinded |
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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.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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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Completion of all analyses of all samples from all patients including data analysis. |
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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 | 11 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 30 |