Sepsis due to community acquired pneumonia Infections and Infestations Sepsis
Conditions
Interventions
Stage 1: Two small groups of patients will receive a single dose of either 50 mg or 100 mg of melatonin.
Stage 2: Patients will be randomly allocated into either:
Group
Sponsors
University of Aberdeen/NHS Grampian (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients who are within 24h of fulfilling the criteria for sepsis with clinical suspicion of community acquired 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 plus systemic inflammatory response syndrome, defined by two or more of the following: 1. Core temperature 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
Exclusion criteria
Exclusion criteria: 1. Anyone 20mg/d prednisolone or equivalent, used regularly for >2 weeks prior to ICU admission) 5. Premenopausal females without a negative pregnancy test or a history of surgical sterilization. 6. Patients receiving fluvoxamine or nifedipine 7. Consent refusal
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Stage 1: Adminstration of 2 oral melatonin doses with no SUSARs Stage 2: Approval by the DMC of dose and dosing interval decisions The ultimate goal of experimental therapies in sepsis is reduced mortality. However, using mortality as an endpoint in a pilot study such as this is clearly not feasible. A panel of biomarkers will be used which are surrogates of outcome from sepsis. All outcomes other than final outcome will be measured daily during the ICU stay. Final outcome is mortality at 28d. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Tissue specific injury markers, cytokines, adhesion molecules and chemokines: IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, pentraxin-3, RANTES, MCP-1, MIP1alpha NGAL, SP-D, MMP-9, VCAM-1, P-selectin and TIMP-1. 2. Key clinical parameters including: heart rate, mean arterial pressure, temperature, acute physiologial and chronic health evaluation (APACHE) II score, length of ICU stay, ICU- and 28 day- all cause mortality, daily sequential organ failure score, time on vasopressor support 3. Time on the ventilator and ventilator settings such as positive end expiratory pressure, peak inspiratory pressure and minute volume 4. Ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FIO2 ratio) All outcomes other than final outcome will be measured daily during the ICU stay. Final outcome is mortality at 28d. | — |
Countries
Scotland, United Kingdom
Contacts
Public ContactHelen Galley
Outcome results
None listed