Early EUS-guided celiac plexus neurolysis versus opioids for the treatment of pain in pancreatic carcinoma

objective: to prospecively compare the efficiency of early EUS/guided celiac plexus neurolysis with conventional transdermal opioid treatent in¨patinets with irresectable pancreatic carcinoma.
study design: randomized multi center(tertiairy referral) study.
Study population; patients with irresecatble pancreatic carcinoma suffering from pain (VAS score>3) not controlled by low dose opioids(equivalent to 50 mcg transdermal fentanyl patches).
Interventions:Patients are randomly assigned to two predefined treatment algorithms. The first is the conventional type of treatment wich consists of (increasing) dosages of transdermalfentanyl patches with rescue CPN only in case of failure of opioids treatment. The second treatment algorithm consists of early (repeated) CPN with increasing dosages of transdermal fentanyl patches only in caseof CPN failure. Adequate treamtment is defined as a pain score<4 on a scale from 0-10 (VAS score) and absence of unmanageable opioid-dependent side effects. The CPN will be performed by means of endoscopic ultrasound(EUS)-FNI (fine needle injection).
Primary outcome parameter:
Quality of Adjusted Life Years (QALYs) Secondary outcome parameters
Health-related quality of life (EORTC-QLQ-C30)(see table 2), Survival, Opioid requirement, Health status (EQ-5D)(table 1 and figure 3), Adverse effects, Costs
power/data analysis: Patients will be randomised 1:1 according to two treatment algorithms. A sample size of 57 in each group will have 80% power to detect a difference in means of 0.05 (the difference between a mean QALY of 0.15 in one group and a mean QALY of 0.10 in the other). Assuming that the common standard deviation is 0.094 (based on a maximum range of QALY values of 0.5) and using a two-group t-test with a 0.05 two sided significance level. To allow for 5% withdrawal 120 patients will be included.

We want to investgate which treatment modality is better, the fentanyl patches or the EUS-guided CPN. This has never been investigated before. We think that the latter treatment might be less effective than one would expect according to earlier studies.

Patients will be randomised according to two treatment algorithms. The first “conventional” type treatment algorithms consists of increasing dosages of transdermal fentanyl patches. In this algorithm, EUS-guided CPN (rescue) will only be performed in case of failure of opioid treatment because of insufficient pain relief (VAS score >=4) or unmanageable side effects. The second treatment algorithm consists of early (repeated) EUS-guided CPN. In case of insufficient pain relief after the second CPN, opioid treatment with transdermal fentanyl patches may be started. Adequate response to therapy (either after EUS-guided CPN or opioids) is defined as a pain score <= 3 on a scale from 0-10 (VAS score) and the absence of unmanageable opioid-related side effects.