None listed
Conditions
Brief summary
Introduction: You are invited to take part in this research project, Systemic fibrinolytic Activity of Intrapleural Alteplase in Pleural Infection. This is because you have a pleural infection (which means that fluid has collected around the lung and is infected) and you are to have Intrapleural Alteplase as part of your standard of care. The research project is aiming to test if a common treatment for pleural infection (Alteplase), will enter the bloodstream and circulate around the body after it is given into the pleural fluid. Purpose: The lung and the inside of the chest wall are both covered by a thin lining called the pleura. Under normal circumstances, this lining produces a very small amount of fluid to lubricate the lung during breathing. Sometimes there can be a build-up of fluid in the space between the pleural linings which gets infected, which is called a pleural infection. These occur in up to 50% of people who have pneumonia (infection of the lung), but are often very small and can’t be seen on a chest x-ray. In many cases, they clear up with antibiotics; less commonly, a chest tube is required to drain the fluid. Sometimes chest drainage is not enough to clear the fluid as a mesh of protein locks away the infected fluid in pockets which the chest tube may not reach. When these protein-pockets happen, people are said to have a complex pleural effusion. To help break down these protein-pockets, sometimes a medication called Alteplase is given through the chest tube. Alteplase has been proven to help people with pleural infection that also have complex pleural effusions, to get better and avoid surgery. It doesn’t appear to be absorbed into the body when given into the pleural space but this hasn’t been proven. We are doing this project to see if this is true or not. It is important to know if Alteplase given into the pleural space enters the blood-stream as it can cause bleeding in other parts of the body if this happens. What does participation involve: There is a list of criteria that must be met in order to participate in the study. The study team believe you meet the study criteria and that is why you have been approached about it. If you agree to the study, you will be participating in a prospective study. You will have 1 additional blood tests per dose of Alteplase compared to normal treatment, taking about 20mls of blood from your veins each time. This will be done 45 minutes after receiving Alteplase. The blood will be taken either by a lung specialist or a specialist nurse. If it is anticipated that there will be difficulty taking these blood sample, a lung specialist will acquire the blood with the help of an ultrasound machine.
Interventions
Pleural infection is associated with significant mortality and morbidity. Historically, pleural infections have been managed with surgical methods. However, intrapleural instillation of tissue-plasminogen activator (tPA) and deoxyribonuclease (DNAse), have been shown to be effective and safe. There remain unanswered questions about intrapleural tPa, in particular the systemic fibrinolytic effects.
This study seeks to measure systemic markers of coagulation and fibrinolysis in people receiving in
Pleural infection is associated with significant mortality and morbidity. Historically, pleural infections have been managed with surgical methods. However, intrapleural instillation of tissue-plasminogen activator (tPA) and deoxyribonuclease (DNAse), have been shown to be effective and safe. There remain unanswered questions about intrapleural tPa, in particular the systemic fibrinolytic effects. This study seeks to measure systemic markers of coagulation and fibrinolysis in people receiving intrapleural therapy at current standard doses. The study will recruit participants (n=50) who are deemed suitable by their treating physician as having a complex pleural infection requiring the instillation of tPa and DNAse. Prior to receiving intrapleural fibrinolytics agents, all patients receive assessment of coagulation factors as they would in standard practice. At this same episode of venepuncture additional serum samples will be sent: Plasminogen activator inhibitor-1 (PAi1) - naturally occurring serine kinase inhibitor that acts as the main inhibitor of tPA Overall haemostatic potential assay (OHP) - measurement of fibrin generation, which represents the interactions between prothrombotic and thrombolytic agents in the serum at the time of collection Plasminogen - target for tPA, which cleaves plasminogen into plasmin which binds to and degrades fibrin (ie. thromboses) Tissue Plasminogen Activator (tPA) - measurement if there is systemic spread of tPa from the pleural space The study will collect serum coagulation data following administration of intrapleural tPA and DNAse on up to three consecutive days. The timing and dosage of which will be decided upon by their treating physician in line with standard practice. The participant will undergo repeat venepuncture 45 minutes post instillation to assess coagulation status as well as the experimental serum tests listed above. It is worth noting that the patient would routinely undergo venepuncture on these days as part of standard care, and such the venepuncture does not amount to a large change from usual practice. Observations of participants will be in the inpatient hospital setting. Observation will begin the day prior to receiving their first dose of intrapleural fibrinolytic agents and cease after the final dose (up to four consecutive days).
Sponsors
Northern Health
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Adult patients (18 years and older) with complex pleural infections requiring intrapleural tPA and DNAse as decided by their treating physician. Complex pleural infection are those infections that do not resolve/drain with antibiotics and thorocostomy tube that may have a loculated/septated appearance on imaging, may have a purulent macroscopic appearance and may have cultured bacteria from pleural fluid.
Exclusion criteria
Individuals that are deemed unsuitable for intrapleural tPA. These include those with active bleeding, current use of an anticoagulant with evidence of affected coagulation status, a medical condition which results in an affected coagulation status or those that are pregnant.
Outcome results
None listed