A therapy combining two existing drugs could provide an effective new approach for treating patients with pleural infections, a serious condition where infected fluid builds up in the space between the ribs and lungs.
The results of a randomised clinical trial called MIST2, published in the New England Journal of Medicine, have shown that two drugs for breaking up the thick pleural fluid, when used together, improve drainage of the fluid from the chest.
Standard treatment for pleural infections involves giving patients antibiotics to treat the infection and a tube inserted into the chest to drain the fluid. But in around a third of cases this treatment fails.
Where treatment fails, options then normally involve surgery to drain the infected fluid, but this is invasive and may not always be suitable for older and more unwell patients where there may be other complications. As well as surgery, it can mean long hospital stays and in some cases, a slow and uncomfortable decline with a mortality rate of more than 20%.
The researchers at Oxford University led by the late Professor Robert Davies, along with colleagues at the MRC Clinical Trials Unit in London, set out to investigate whether two agents to break down components in the infected pleural fluid would help drainage and improve outcomes for patients.
They conducted a trial in which 210 adult patients at 11 UK centres were randomised to receive one of four study treatments for three days: placebo; Alteplase (t-PA) alone; DNase alone; or both t-PA and DNase.
The two drugs when used together showed significantly improved drainage of the fluid from the chest, the primary outcome measure for the trial.
Over the course of a week, patients receiving both drugs saw a 30% reduction in fluid volume seen in their chest X-rays, compared to 17% for the placebo group. There was no effect above placebo for either drug on its own.
The number of patients referred for surgery over the next three months was also significantly lower for those receiving both drugs, and the average hospital stay was between 6 and 7 days less compared to the placebo group. Any adverse events did not differ in frequency between study groups, suggesting the treatment is safe for these patients.
Dr. Najib Rahman of Oxford University said:
"We've shown that the therapy clearly improves drainage of fluid in patients with pleural infection. But we still need to be cautious - it is not yet certain whether clearance of the chest X-ray translates into important outcomes for patients, like reduced surgery rates, fewer fevers, and shorter stays in hospital. Although our results strongly suggest this is the case, larger studies are now needed to confirm this."