The Second Therapeutic Intervention in Malignant Effusion Trial
A randomised controlled trial to assess the efficacy and safety of patient controlled malignant pleural effusion drainage by indwelling pleural catheter compared to chest drain and talc slurry pleurodesis.
• The study ran from 2007 to 2011
• NIHR recruited 106 patients to the total 114 patients recruited to the trial
• 6 sites recruited to the trial
• Funders: British Lung Foundation
• NIHR CRN successfully recruited a large proportion of patients onto the trial
• Chief Investigator: Professor NajibRahman
• The results of this study has changed the treatment approach for thousands of patients with malignant pleural effusion around the world. The BTS guidelines are due to be updated to reflect the results of the TIME2 trial in 2019.
Patients with cancer that has spread (metastasised) often have fluid collecting in the space between the lungs and the chest wall. This is called malignant pleural effusion and affects more than 50,000 people every year in the UK. With as much as three litres of fluid collecting around the lungs, it causes difficult and unpleasant symptoms such as breathlessness, excessive coughing and it can be very painful for patients. The condition signals incurability of the cancer, shortens life expectancy and severely compromises quality of life for the patient. The British Thoracic Society (BTS) Evidence Based Guidelines published in 2010 stated that the first line of treatment for patients with this condition was talc slurry pleurodesis. This is when doctors drain the fluid off and then seal the cavity, using a drug which is given into a chest drain.
Pleurodesis is effective in treating about 70 per cent of patients, but is often very painful for the patient, means a hospital stay of five to seven days to do the procedure and the fluid is often back within a couple of weeks. The recommended second line of treatment in 2010, was a procedure called Indwelling Pleural Catheter. This is when a special chest catheter (or tube), called an Indwelling Pleural Catheter (IPC), allows patients to drain the fluid that collects around their lungs at home.
This means that they don’t have to have a pleurodesis and may be able to control their breathlessness better, too. This trial compared whether using an IPC helped people to control their breathlessness more effectively than the usual treatment (pleurodesis). People who took part were randomised to either pleurodesis or an IPC. It compared the safety of these two treatments, the quality of life, hospital stay and any adverse events of those taking part.
Outcomes and findings
This was the first randomised controlled trial to directly compare IPCs with chest tube and talc slurry pleurodesis for initial treatment of malignant pleural effusion. The results of the trial showed that both treatments were effective at initially treating patients malignant pleural effusion and there was also no significant difference in the outcome measure of chest pain and quality of life improvements between the two treatments.
In terms of length of hospital stays, adverse events and the inconvenience of ongoing drainage could be important factors in patient and doctor choice of the inital treatment of malignant pleural effusion. The result of the trial changed the current British Thoracic Society guideline treatment approach to offer both treatment options as a first line of treatment for malignant pleural effusion. This trial has been integral to the new guidelines published by the American Thoracic Society and the European Respiratory Society on malignant pleural effusion.
Value to the NHS
Both treatment options require the procedure to take place in hosptial, however the IPC option takes much less time to do, approximately two hours and can be done as an out-patient. Whilst the talc slurry pleurodesis procedure requires a stay of up to 7 days in hospital. The 30 per cent failure rate of the talc slurry pleurodesis within one to two weeks of having the initial procedure, meant that patients were often required to have the procedure done again, increasing their time in hospital. Although this trial did not measure a cost saving benefit to the NHS, it could be argued the additional bed days required by having the procedure done again saved the NHS 25,000 bed days and approximately a £10 million saving from NHS budgets.
“This trial altered the treatment approach as stated in the BTS guidelines around Malignant Pleural Effusion. This now provides better patient choice for treatment of the condition. It was also an acorn study for more trials to take place into the condition. “The support of the NIHR was hugely valuable, that without it, the clinicians on the study would not have been able to recruit the required patients.”
Professor Najib Rahman, Chief Investigator for TIME2.
• The second therapeutic intervention in malignant effusion trial (TIME2). European Respiratory Journal http://erj.ersjournals.com/content/40/Suppl_56/3074
• Management of Malignant Pleural Effusions. An Official ATS/STS/STR Clinical Practice Guideline. NCBI https://www.ncbi.nlm.nih.gov/pubmed/?term=ats+mpe#
• ERS/EACTS statement on the management of malignant pleural effusions. NCBI https://www.ncbi.nlm.nih.gov/pubmed/?term=ers+mpe#