Early intrapleural enzyme therapy for pleural infection shortens pain, recovery time

Key takeaways:

• A phase 3 trial evaluating intrapleural enzyme therapy vs. video-assisted thoracoscopic surgery is feasible.
• Early intrapleural enzyme therapy may be more beneficial for patients with pleural infection.

Patients hospitalized with pleural infection reported better health and less pain 2 months after receiving intrapleural enzyme therapy vs. video-assisted thoracoscopic surgery, according to study results.

Additionally, both intrapleural enzyme therapy (IET) and video-assisted thoracoscopic surgery (VATS) reduced the duration of hospitalization vs. standard care, according to researchers.

“This is the first multicenter [randomized controlled trial] of early intrapleural enzyme therapy vs. early surgery in pleural infection,” Eihab O. Bedawi, PhD, MBBS, consultant respiratory and pleural physician at Sheffield Teaching Hospitals, and colleagues wrote. “It demonstrates the feasibility of recruitment and a potential shortening of [length of stay] with VATS, but also signals toward earlier resolution of pain and return to usual function with IET.”

In a prospective multicenter randomized controlled trial (MIST-3) published in American Journal of Respiratory and Critical Care Medicine, Bedawi and colleagues analyzed 60 patients with a pleural infection randomly assigned to either continued standard care (n = 21), early IET (n = 19) or early VATS (n = 20) to see if randomization can meet predefined feasibility criteria and to compare the two interventions.

All patients received standard care involving chest tube drainage and antibiotics before being randomly assigned to one of the groups.

At baseline, all three groups had comparable demographic, clinical and microbiological characteristics, according to researchers.

All included patients retained to discharge, meeting the feasibility criteria of more than 95%. Additionally, researchers’ percentage criteria for 2 weeks of follow-up was met since it was above 80% (84.5%).

Following discharge, one patient assigned standard care and one patient assigned IET withdrew from the trial.

Most patients completed the Hospital Anxiety and Depression Scale (HADS) within 1 to 2 days after randomization (93%), whereas a lower percentage of the total cohort completed the International Physical Activity Questionnaire (IPAQ; 79%) and EuroQol five-dimension health utility index (EQ-5D-5 L; 81%) at 2 weeks.

The IET group had the greatest proportion of patients who achieved treatment compliance (73.6%), followed by the VATS group (50%) and the standard care group (47.6%).

Patients randomly assigned to IET had a significantly shorter median time to intervention than patients randomly assigned to VATS (1 day vs. 3.5 days; P = .02).

Between the two intervention groups (IET and VATS) and the standard care group, researchers found no significant difference in median length of stay (7 days vs. 10 days).

The same outcome was found when researchers assessed 2-month readmission and additional intervention; however, they noted “the study was not adequately powered for this outcome.” Following discharge, each group had a small proportion of patients readmitted to the hospital, including 23.8% of the standard care group, 26.3% of the IET group and 30% of the VATS group.

Of the total cohort, four patients from the VATS group died at 12 months (two deaths prior to discharge), whereas only one patient each from the IET group and the standard care group passed away at this checkpoint.

Notably, three of the four patients from the VATS group who died did not receive the surgery, according to researchers.

In terms of changes in health over the course of 2 months, more improvement was found among patients assigned to early IET (mean EQ-5D utility index score, baseline, 0.35; 2 months, 0.83) vs. VATS (baseline, 0.38; 2 months, 0.59; P = .023).

The difference in change in mean EQ-5D 100-mm VAS scores was not significant between VATS and standard care, but researchers found significantly more improvement among patients assigned to IET (baseline, 45.1; 2 months, 79.5) vs. standard care (baseline, 49.9; 2 months, 63.6; P = .027).

Between the three groups, mean HADS scores collected 1 to 2 days after randomization and pain scores 2 months after discharge did not significantly differ, but researchers noted that the greatest decline in pain scores was found in the IET group.

“We fully accept that a much larger study with longer follow-up would be needed to provide reliable evidence in regard to mortality, quality of life improvement and long-term survival between IET and surgery,” Bedawi and colleagues wrote. “Based on the results of the MIST-3 study, a further definitive phase 3 study is being developed that does not include a standard care arm.”