Neoplasms

Digestive System Diseases

All Conditions

Biliary Tract Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

All patients who underwent endoscopic radiofrequency ablation with the HabibTM EndoHBP as a treatment for malignant biliary obstruction in Austria between November 2010 and December 2012.

Endoscopic radiofrequency ablation with the HabibTM EndoHBP catheter uses bipolar electrical energy for tissue coagulation and can be applied without any special patient preparation in the context of an endoscopic retrograde cholangiopancreatography (ERCP) examination to treat malignant biliary strictures.

Endoscopic radiofrequency ablation

ERCP is used to guide the RFA-catheter under radiological control to the location of the malignant stricture.

Endoscopic retrograde cholangiopancreatography (ERCP)

Used to apply radiofrequency energy to the malignant biliary stricture (see also intervention "endoscopic radiofrequency ablation")

HabibTM EndoHPB catheter

Werner Dolak, MD

Biliary obstruction is importantly influencing quality of life and survival of patients suffering from primary or secondary bile duct malignancies. The aim of this retrospective data analysis is to evaluate endoscopic radiofrequency ablation (RFA) with the HabibTM EndoHBP catheter for the treatment of malignant biliary obstruction. RFA procedures performed in Austria so far will be analyzed with regard to feasibility and safety of the technique. Therefore, the following parameters will be assessed: (among others) technical failures during the RFA procedure, complications during the RFA procedure, hospital stay, adverse events during hospital stay and until first clinical control after discharge (an expected average of 4 weeks after RFA procedure), 30-day and 90-day mortality. The results of this study should help to better understand important aspects of biliary RFA which may positively influence future applications of this method.

Introduction

Biliary obstruction is the most relevant life limiting factor in patients suffering from primary or secondary bile duct malignancies. Underlying tumors, such as extrahepatic cholangiocarcinoma (CCa) of Klatskin type, pancreatic adenocarcinoma or metastases of colorectal cancer, are often diagnosed at an advanced stage when presenting with biliary obstruction. This mostly restricts treatment strategies to palliative management. Within this setting the prevention of biliary complications like jaundice, cholangitis or cholangiosepsis is one of the therapeutic key factors to extend survival and maintain quality of life \[De Groen, Skipworth\]. Endoscopic stenting of the biliary tract is an easy and safe approach to restore biliary drainage \[Smith\]. Self-expanding metal stents are preferred to plastic stents because of the lower risk of stent occlusion \[Kaassis, Soderlund\]. In addition to stenting endoscopic therapies that directly affect the local tumor mass, have been developed within the past years. First of all, photodynamic therapy using different photosensitizers has shown promising results for the reduction of tumor size and maintenance of biliary drainage \[Ortner, Zoepf\]. However, the patient management for this treatment involving peri-interventional photosensitivity remains cumbersome.

Recently, an endoscopically applicable radiofrequency catheter for the biliary tract, the so called HabibTM EndoHBP catheter, was introduced into the market. It uses bipolar electrical energy for tissue coagulation and can be applied without any special patient preparation in the context of an endoscopic retrograde cholangiopancreatography (ERCP) examination. RFA is well known from transcutaneous applications, where it already proved to be effective as a treatment option for hepatocellular carcinoma or intrahepatic CCa \[Minami\]. The new HabibTM EndoHBP catheter was already evaluated ex vivo \[Itoi\] and showed promising results concerning safety and prevention of stent occlusion in the context of one small retrospective clinical study \[Steel\].

Primary objective

Feasibility and safety of endoscopic radiofrequency ablation with the HabibTM EndoHBP catheter for the treatment of malignant biliary obstruction

Study Design

Retrospective analysis of prospectively gained clinical data

Primary endpoint

Technical failures during the RFA procedure

Secondary endpoints

1. Complications during the RFA procedure
2. Hospital stay
3. Adverse events during hospital stay and unil first clinical control after discharge (an expected average of 4 weeks after RFA procedure)
4. 30-day and 90-day mortality

Study Population

All patients who underwent endoscopic radiofrequency ablation with the HabibTM EndoHBP as a treatment for malignant biliary obstruction between November 2010 and December 2012 in Austria.

Methods

Endoscopic examination report databases will be screened for "radiofrequency ablation" in the context of an "endoscopic retrograde cholangiopancreatography" to identify the mentioned study population. Examination reports, discharge letters and patient curves of the study patients will be screened to yield the following parameters:

* Demographics

  * Sex
  * Age at first RFA-intervention
* Underlying disease that led to malignant biliary obstruction

  * Type of underlying disease
  * Time from diagnosis to first RFA-intervention
  * Previous treatment attempts (chemotherapy, radiation therapy, photodynamic therapy)
* Procedure related parameters

  * Prior biliary stents (type, amount)
  * Date of RFA procedure
  * Amount of RFA-applications during the procedure (energy, time)
  * Technical failure of the RFA catheter during the RFA procedure (defined as any technical problem that hinders the satisfactory application of RFA)
  * Complications during the RFA procedure (defined as any adverse change from the subject's baseline condition, i.e. any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician, whether or not considered related to the medical device)
  * Stenting after the procedure (type, amount)
* Post-interventional parameters

  * Days of hospitalization after the RFA procedure
  * Adverse events during hospital stay and until first clinical control after discharge (an expected average of 4 weeks after RFA procedure) defined as any adverse change from the subject's baseline condition, i.e. any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician, whether or not considered related to the medical device
  * Survial status (dead/alive) at the time of the data collection
  * (Cause of death)
  * (Time between first RFA procedure and death)

Data processing will be done after pseudonymization using continuous patient identification numbers. All parameters will be assessed descriptively. For scaled parameters (e.g. age) median and range will be calculated, for nominal parameters (e.g. type of underlying disease) the proportions of sub-items will be reported. Mortality will be assessed creating a Kaplan Meyer curve. 30-day and 90-day mortality will be extrapolated from this curve. All data processing will be done with SPSS 19.0.

Risk/Benefit assessment

Due to its retrospective design this study does not inherit any risk for the study patients.

Expected impact and Outlook

The results of this study may help to better understand the feasibility and safety profile of endoscopic radiofrequency ablation with the HabibTM EndoHBP catheter with potential effects on future applications.

Radiofrequency Ablation for Malignant Biliary Obstruction

Endoscopic Radiofrequency Ablation for Malignant Biliary Obstruction

Duration of hospitalization after the performance of RFA.

Adverse events occuring within 30 days after the RFA-procedure, defined as any adverse change from the subject's baseline condition, i.e. any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease which is considered to be clinically relevant by the physician, whether or not considered related to the medical device.

Deaths occuring within 30 and 90 days after the RFA-procedure.

The technical feasibility in this study will be specified as ratio of all technically successful RFA-applications to all examinations in which RFA-use was intended. A RFA-application will be classified as technically successful if it is possible to introduce the RFA-catheter into the biliary system, place it adequately accross the malignant stricture, apply RFA-energy and withdraw the RFA-catheter after RFA-application.

Clinically relevant complications occuring during the use of RFA, defined as any adverse change from the subject's baseline condition, which is considered to be clinically relevant by the physician, whether or not considered related to the medical device (e.g. bleeding, perforation).

Medical University of Vienna

Principal Investigator

Gland and Hormone Related Diseases

Symptoms and General Pathology

Rare Diseases

Cholangiocarcinoma

Pancreatic Neoplasms

Pancreatitis

Choledocholithiasis

Pancreatic Diseases

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Bile Duct Diseases

Common Bile Duct Diseases

Gallstones

Cholelithiasis

Cholecystolithiasis

Pancreatic Cancer

Bile Duct Cancer

Adjuvants, Anesthesia

Central Nervous System Depressants

Psychotropic Drugs

All Drugs and Chemicals

Analgesics

Midazolam

Meperidine

Etomidate

Anesthetics

Hypnotics and Sedatives

Anti-Anxiety Agents

Anesthetics, Intravenous

Anesthetics, General

GABA Modulators

Neurotransmitter Agents

Analgesics, Opioid

Narcotics

This cohort would be administered etomidate with meperidine. The initial dose of etomidate is 0.1mg/kg IV and meperidine, 25mg. Additional dose of etomidate is 2mg(1cc). In old age cased, more than 65 years old, 30% of initial dose discounted.

This cohort would be administered midazolam with meperidine. The initial dose of midazolam is 0.06mg/kg IV and meperidine 50mg IV. Additional dose is 1mg of midazolam. In the elders, more than 65 years old, initial dose was declined to 70%.

Both groups were administered same dose of meperidinie 50mg. Then elders \> 80 years old were administered 25mg iv bolus.

BYUNG HYO CHA, Dr.

Recently up-coming drug, etomidate which is a modulator of GABA(gamma-Aminobutyric acid)-A receptor has been known that it maintains the appropriate sedative levels and affects little effects on respiratory system.

The investigators are now trying to investigate that etomidate with meperidine combination regimen is superior to the midazolam with meperidine more effective and less harm on sedation during the ERCP procedure.

ERCP (Endoscopic retrograde cholangiopancreatogram) is an uncomfortable and time-consuming procedure compared to other endoscopic procedures. Most ERCP procedure had been performed in sedation using tranquilizers and pain-killers.

Until recently, midazolam and opioid combination regimen recognized as a standard therapy is widely used, but the sedative effect is insufficient and intermittent paradoxical reaction has been questioned. Another drug, such as propofol, has been known that the sedative effect is superior one of the midazolam but disappointed due to narrow therapeutic range of respiratory distress and absence of antagonist. Meanwhile, recently up-coming drug, etomidate which is a modulator of GABA-A receptor has been known that it maintains the appropriate sedative levels and affects little effects on respiratory system.

For these advantages, this short acting sedative drug has been widely used in the emergency room during minor operation and in the operation room for induction. However, research on the efficacy during ERCP was not yet published.

In this regards, the purpose of the investigators study is to prove the efficacy of etomidate for sedation and to establish new evidence based sedation guidelines during ERCP procedure.

Etomidate vs. Midazolam for Sedation During ERCP

Etomidate With Meperidine vs Midazolam With Meperidine for Sedation During Endodscopic Retrograde Cholangiopancreatogram (ERCP)

The frequency of intervention which was defined as any restraint of the patient's head, arms, or legs if they became agitated, or if patient movement was not controlled with verbal instruction from the endoscopist during the whole intraoperative phases.

Hypoxia defined as peripheral blood oxygen saturation measured by pulse oxymeter \< 90%

Cheju Halla General Hospital

Director of Endoscopy clinic, Digestive Disease Center, Department of Internal Medicine

Additional probable side events, such as, paradoxic reaction in MDZ group, and myoclonus in ETM group were counted during the whole 3 phases of procedure.

This cohort would be administered etomidate with meperidine. The initial dose of etomidate is 0.1mg/kg IV and meperidine, 25mg. Additional dose of etomidate is 2mg(1cc). In old age cased, more than 65 years old, 30% of initial dose discounted.

Etomidate: This cohort would be administered etomidate with meperidine. The initial dose of etomidate is 0.1mg/kg IV and meperidine, 25mg. Additional dose of etomidate is 2mg(1cc). In old age cased, more than 65 years old, 30% of initial dose discounted.

Meperidine: Both groups were administered same dose of meperidinie 50mg. Then elders \> 80 years old were administered 25mg iv bolus.

This cohort would be administered midazolam with meperidine. The initial dose of midazolam is 0.06mg/kg IV and meperidine 50mg IV. Additional dose is 1mg of midazolam. In the elders, more than 65 years old, initial dose was declined to 70%.

Midazolam: This cohort would be administered midazolam with meperidine. The initial dose of midazolam is 0.06mg/kg IV and meperidine 50mg IV. Additional dose is 1mg of midazolam. In the elders, more than 65 years old, initial dose was declined to 70%.

Meperidine: Both groups were administered same dose of meperidinie 50mg. Then elders \> 80 years old were administered 25mg iv bolus.

Total

Age, Continuous

Sex: Female, Male

Body Mass Index (kg/square of m.)

Procedure Time (min)

1. To standardize proper sedation level we used Ramsay Sedation Scale but this scale could be calculated subjectively.
2. Double blindness was not applied strictly because of quite different pharmacodynamics of two experimental drugs.

Dr. Byung Hyo Cha, Director of ETOMI-1 study

If the true difference in the experimental and control means is 4, total 26 experimental subjects and 26 control subjects was required to reject the null hypothesis that the means of the primary outcome values of experimental and control groups are equal with probability (power) 0.8. The Type I error probability associated with this test of this null hypothesis is 0.05.

Number of Intervention

All the continuous variables were compared using the Mann-Whitney U test and dichotomous categorical variables was used and the Pearson chi-square with Fisher exact test. We used the linear mixed model to compare the differences of paired data, such as mean values of RR, SpO2, MAP, HR, and RSS at different time points of the two different sedation groups. For two-sided tests, p \< 0.05 was considered statistically significant.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Radiofrequency Ablation for Malignant Biliary Obstruction	NCT01758341	Biliary Tract N...	Endoscopic radi... Endoscopic retr... HabibTM EndoHPB...	18 Years -	Medical University of Vienna
Etomidate vs. Midazolam for Sedation During ERCP	NCT02027311	Choledocholithi... Cholangiocarcin... Pancreatitis Pancreatic Canc...	Etomidate Midazolam Meperidine	20 Years - 90 Years	Cheju Halla General Hospital
Radiofrequency Ablation for Malignant Biliary Obstruction	NCT01758341	Biliary Tract N...	Endoscopic radi... Endoscopic retr... HabibTM EndoHPB...	18 Years -	Medical University of Vienna

Spots Global Cancer Trial Database for endoscopic retrograde cholangiopancreatography (ercp)