The premature closure of ROMPA clinical trial: mortality reduction in septic shock by plasma adsorption

Abstract

Objectives: Coupled Plasma Filtration and Adsorption (CPFA) use in septic shock remains controversial. The objective is to clarify whether the application of high doses of CPFA in addition to the current clinical practice could reduce hospital mortality in septic shock patients in Intensive Care Units at 28 days and at 90 days follow-up.

Design: We designed a prospective randomised clinical trial, Reducción de la Mortalidad Plasma-Adsorción (ROMPA), to demonstrate an absolute mortality reduction of 20% (α=0.05; 1-β=0.8; n=190 (95×2)).

Setting: Being aware of the pitfalls associated with previous medical device trials, we developed a training programme to improve CPFA use (especially clotting problems). The protocol was approved by the ethics committees of all participating centres. Circumstances beyond our control produced a change in recruitment conditions unacceptable to ROMPA researchers and the trial was discontinued.

Participants: By closure, five centres from an initial 10 fulfilled the necessary trial criteria, with 49 patients included, 30 in the control group (CG) and 19 in the intervention group (IG).

Intervention: CPFA.

Main outcome measures: Hospital mortality at 28 days and 90 days follow-up.

Results: After 28 days, 14 patients died (46.7%) from the CG and 11 (57.9%) from the IG, not reaching statistical significance (p=0.444). At 90 days, 19 patients had died (63.3%) from the CG and 11 patients (57.9%) from the IG, (p=0.878). The adjustment by propensity score or the use of the Kaplan-Meier technique failed to achieve statistical difference, neither by Intention to Treat nor by the Actual Intervention Received.

Conclusion: We herewith present the results gained from the prematurely closed trial. The results are inconclusive due to low statistical power but we consider that this data is of interest for the scientific community and potentially necessary for any ensuing debate.

Register: NCT02357433 in clinicaltrials.gov.

Keywords: adult intensive & critical care; clinical trials; infectious diseases.

Figure 1

Flow chart of the clinical trial (partial results).

Figure 2

Survival analysis using the Kaplan-Meier estimator comparing both groups. Red, intervention; blue, control. A, intention to treat; B, real intervention.