3.1 The key clinical outcomes for the PleurX peritoneal catheter drainage system presented in the decision problem were:
technical success of catheter insertion and drainage procedure
resolution of symptoms (bloating, nausea, acid reflux, reduced appetite, negative perception of body image and resulting psychological distress)
quality of life outcomes
adverse events (catheter site infections, peritonitis, catheter occlusion, and haemorrhage or bowel perforation when the device is inserted)
resource use outcomes, for example re-admission rates, re-interventions and duration of hospital stay.
3.2 The clinical evidence for the PleurX peritoneal catheter drainage system was based on 9 observational studies (10 manuscripts), 2 of which were conducted in the UK. Six studies were case series with 10 or more patients, one study was a qualitative case series (4 patients), and there were 3 case reports (4 or fewer patients). The external assessment centre considered all the studies identified by the sponsor to be relevant and did not identify any further studies.
3.3 Rosenberg et al. (2004) conducted a single-centre, retrospective, comparative case series. It evaluated treatment complication rates in patients whose malignant ascites was managed using the PleurX peritoneal catheter drainage system (n=40 patients and catheters) compared with inpatient large-volume paracentesis (n=67 patients, 392 procedures). Overall complication rates (using number of patients rather than number of procedures) were the same for both procedures: 7.5% (3 of 40; 95% confidence interval [CI] 1.6% to 20%) for the PleurX peritoneal catheter drainage system and 7.5% (5 of 67; 95% CI 2.2% to 15%) for large-volume paracentesis. In patients whose ascites was managed with PleurX, complications were infection (n=1), leakage (n=1) and loculations (n=1), and all catheters were subsequently removed. Large-volume paracentesis complications were peritonitis (n=3) and loculations (n=2). The PleurX peritoneal catheter patency rate (defined as the number of catheters known to be functioning at death, study end or resolution of ascites) was 67.5% (n=27); however 11 (27.5%) patients were lost to follow-up.
3.4 Courtney et al. (2008) carried out a multi-centre, single-arm, prospective case series evaluating treatment outcomes in 34 patients with malignant ascites treated with the PleurX peritoneal catheter drainage system over a 12 week follow-up period (or until death in some patients). It reported 100% technical success during the placement procedure (defined as intraperitoneal positioning of the device and the ability to withdraw ascitic fluid from the device at the completion of the procedure), with one minor procedural complication. Twenty patients experienced complications during the follow-up period including minor complications that resolved spontaneously. Two catheters needed to be removed, and other complications were infection (n=2), occlusion/loculations (n=4), leakage of ascitic fluid (n=7), dizziness (n=5), shortness of breath (n=1) and severe anaemia (n=1). Available records from 19 patients showed that the mean number of drainage sessions after placement of the PleurX peritoneal catheter was 23.3 per patient (range 5–56), and that of the total 433 sessions, 13% were performed by a nurse, and the remainder were carried out by the patient alone (28%) or a carer (58%). The catheter patency rate was 85% (n=29); the remaining 5 patients were lost to follow-up. Changes in symptom severity between baseline and at 2, 8 and 12 weeks were assessed using a validated tool. There was a reduction in the severity of abdominal discomfort, bloating, diarrhoea and nausea at 2 and 8 weeks. An overall improvement in quality of life at 12 weeks was reported in 28% of respondents.
3.5 In a single-arm retrospective case series study, Mullan et al. (2011b) evaluated the procedural safety, mean survival, long-term efficacy, long-term complication profile and cost benefit of the PleurX peritoneal catheter drainage system in the management of recurrent malignant ascites (n=50 patients, 52 catheters; 2 patients had their catheters re-inserted). On average, 5.3 inpatient large-volume paracentesis drainage procedures were performed before PleurX peritoneal catheter insertion. A 100% procedural success rate was reported. A mean patient survival of 59.4 days (range 4–216 days) and 165 days (range 29–1036 days) was reported after the PleurX peritoneal catheter insertion and after the first inpatient large-volume paracentesis procedure respectively. The average hospital stay for patients having inpatient large-volume paracentesis was 2.8 days (range 1–6 days; n=23) and the average ascitic fluid drainage per episode of paracentesis was 9.2 litres. Eight patients experienced complications after insertion of the PleurX peritoneal catheter, which were peritonitis (n=1), lymphangitis (n=1), occlusion/loculations (n=3), ascitic leakage (n=1), displacement (n=1) and pain (n=1); one catheter needed to be removed. Primary or secondary catheter patency at death was 100%, with management of complications augmented by multi-modality imaging and fibrinolysis of malfunctioning catheters.
3.6 In a single-arm retrospective case series study (n=10 patients and catheters), Richard et al. (2001) evaluated the clinical outcomes after PleurX peritoneal catheter insertion in patients with treatment-resistant, recurrent malignant ascites. They reported 100% procedural success. Two patients experienced complications, which were occlusion/loculations (n=1) and displacement (n=1). The average time catheters remained in place was 70 days (range 1–100 days).
3.7 In a single-arm retrospective case, Tapping et al. (2011) evaluated the clinical outcomes after PleurX peritoneal catheter insertion in 28 patients (32 catheters) with treatment-resistant, recurrent malignant ascites. A technical success rate of 100% was reported. There were 12 complications, which comprised minor catheter site infections (n=5), ascitic leakage (n=1), displacement (n=4), hernia (n=1) and one further complication that was not described. No catheters needed to be removed other than those that were inadvertently dislodged. The catheters remained in place for an average of 113 days (range 5–365 days) and catheter patency was 86% (24 of 28).
3.8 Saiz-Mendiguren et al. (2010) conducted an observational descriptive case series study of patients (n=10) who had the PleurX peritoneal catheter inserted. They analysed the duration of the procedure, pain reported by the patient during the procedure (using a visual analogue scale score), short- and long-term complications, median patency of the catheter, and the volume of ascitic fluid drained at home (reported by telephone or during consultation). The technical success rate of the insertion procedure was 100%. Two patients reported discomfort during the procedure (visual analogue scale scores 2 and 3 out of 10). No complications were reported during or after the procedure. In one patient with generalised sepsis thought to be caused by a venous cannula, the PleurX peritoneal catheter was removed 58 days after placement as a precaution. Nine patients died; their catheters remained patent for a median of 52 days (range 13–113 days). At the end of the study, one patient remained alive with a patent catheter 124 days after placement. The mean ascitic fluid drainage reported by patients or their carers was approximately 1 litre (one vacuum bottle) every 2–10 days.
3.9 Day et al. (2011) conducted a small qualitative case study, which is currently available in abstract form, and from which the committee considered detailed findings presented as academic-in-confidence data. Patients who had inpatient large-volume paracentesis were also included in the study, but no comparisons were drawn between the 2 treatment groups. Patient opinions and experiences were described in a narrative form and categorised into emergent themes following semi-structured interviews. The results revealed a positive trend of opinion towards PleurX, particularly relating to symptom improvement and increased convenience. All patients were reported to be glad that they had had the PleurX peritoneal catheter inserted. Some negative opinions were expressed including the fact that some patients did not like seeing the ascitic fluid, and others felt that the PleurX peritoneal catheter drainage system made them feel 'more of a patient'.
3.10 Three case reports relevant to the decision problem were also identified. Brooks et al. (2006) described one patient who had had a PleurX peritoneal catheter in place for 18 months and had developed 3 complications: drain blockage (immediately relieved by flushing), hernia around the catheter site, and the presence of gram-negative bacilli in urine and ascites (treated successfully with ciprofloxacin). Iyengar et al. (2002) described 3 patients who had catheters in place for 6, 7 and 12 weeks. One patient experienced dehydration, and one catheter was removed as a precaution in a patient with sepsis. Mullan et al. (2011a) reported experiences of 4 patients taken from a larger study (Mullan et al. 2011b) in whom streptokinase fibrinolytic therapy was successfully used to treat loculations.
3.11 The committee concluded from the available clinical evidence that the PleurX peritoneal catheter drainage system is effective in the palliative management of treatment-resistant, recurrent malignant ascites. It has a high procedural success rate, a low complication rate and the potential to improve patient quality of life.
3.12 Patients with malignant ascites have a disability as defined by the Equality Act 2010. The committee recognised that treatment-resistant, recurrent malignant ascites often has an adverse impact on patients' activities of daily living, which may be improved with the PleurX peritoneal catheter drainage system. The committee was advised by the patient and clinical experts that improvement in quality of life is mainly a result of avoiding regular hospital visits and inpatient stays associated with large-volume paracentesis, and alleviation of symptoms associated with massive ascites through the frequent drainage of small volumes of ascitic fluid.
3.13 The committee recognised the uncertainty about the point in the care pathway at which it would be clinically appropriate to treat patients with treatment-resistant, recurrent malignant ascites with the PleurX peritoneal catheter drainage system. Tapping et al. (2011) considered that patients who had had at least 3 previous large-volume paracentesis procedures would be suitable for treatment with the PleurX peritoneal catheter drainage system, whereas Courtney et al. (2008) inserted the PleurX peritoneal catheter in patients who had had at least 2 large-volume paracentesis procedures in the previous 30 days. The committee considered that the decision to start treatment with the PleurX peritoneal catheter drainage system should be shared between clinicians and patients.
3.14 The committee was advised that the term 'treatment-resistant' is normally understood by clinicians to mean that there is a low likelihood of further medical or oncological interventions (particularly chemotherapy) being successful in preventing or reducing re-accumulation of ascites.
3.15 The committee acknowledged that the current evidence is based on observational studies, with very limited data available comparing the PleurX peritoneal catheter drainage system with other treatments.
3.16 The committee noted that there are 2 ongoing clinical trials using the PleurX peritoneal catheter drainage system. One is investigating the impact on quality of life and the other is comparing early stage PleurX peritoneal catheter insertion with standard large-volume paracentesis. Both trials are expected to be completed in 2012.