Nasobiliary Drain Assisted EUS-guided Gastroenterostomies in Unresectable Malignant Gastric Outlet Obstruction (PENGUIN)

• ClinicalTrials.gov Identifier: NCT04660695
• Recruitment Status: Completed
• First Posted: December 9, 2020
• Last Update Posted: May 14, 2021
• Sponsor: Hospital del Río Hortega
• Collaborators: Hospital General Universitario de Alicante; Clinica Universidad de Navarra, Universidad de Navarra; Complejo Hospitalario de Navarra; Christian Medical College, Vellore, India
• Information provided by (Responsible Party): Francisco Javier Garcia Alonso, Hospital del Río Hortega

Study Description

Brief Summary:

Gastric outlet obstruction in malignant disease appears when the tumor affects the gastroduodenal area, precluding the passage of food into the small bowel. This condition severely affects the quality of life. In patients with unresectable tumors, there are various available treatments:a surgical bypass connecting the stomach to the small bowel, placing a stent through the tumor to widen the passage and creating a gastrointestinal bypass with a lumen apposing metal stent. These stents are deployed with an echoendoscope, which allows to identify a small bowel loop and to deploy the stent, connecting the small bowel and the stomach. This is called a EUS-guided gastroenterostomy (EUS-GE).

EUS-GE is a rather novel procedure. Various techniques to create EUS-GE have been proposed. In this study, the investigators will retrieve data from the procedure and during the thirty following days from consecutive patients undergoing an EUS-GE. The objectives of the study are:

• To perform a detailed step by step description of the nasobiliary drain assisted EUS-GE
• To describe the adverse events encountered
• To describe the proportion of clinical and technical success
• To assess its impact on the patients' quality of life.
• To assess the evolution of the oral intake during the first month after the procedure

Condition or disease	Intervention/treatment
Gastric Outlet Obstruction; Gastric Cancer; Pancreatic Cancer	Device: EUS-guided gastroenterostomy

Detailed Description:

DESIGN

Prospective multicenter case series

AIMS

Primary aim To describe the proportions of technical and clinical success. To describe different variants in the nasobiliary drain assissted EUS-GE technique, offering a detailed step by step description of the procedure performance by different endoscopists

Secondary aims:

To describe the adverse encountered, their severity according to ASGE standards and their management.

To describe the time elapsed between the procedure and the initial oral intake.

To describe the evolution of the oral intake during the first month after the procedure To assess the impact of the operators experience on procedure times, adverse events and technical issues.

To assess the impact of the procedure on the quality of life of the participating patients.

STUDY POPULATION

All consecutive patients over 18 years of age receiving a nasobiliary drain assisted EUS-GE for unresectable malignant GOO are eligible to participate in this study. Patients with a previous gastroduodenal surgery, a previous endoscopic or surgical treatment for GOO, a simultaneous malignant biliary obstruction requiring endoscopic treatment, a distal bowel obstruction, ascites grade 2 or superior, uncorrectable coagulation disorders (INR>1,5) or severe thrombocytopenia (<50000 platelets/mm3). or unable to understand the questionnaires will be excluded.

INTERVENTION

At inclusion

Informed consent will be obtained. A clinical interview and a physical examination will be performed. TheEuropean Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 (EORTC-QLQ-C30), which includes 30 items covering a global health status scale, five functional scales and ten symptom scales will be assessed in a telephone interview.

Endoscopic procedure

All procedures will be performed under sedation. An assistant endoscopist or research nurse will retrieve all data regarding the procedure. Firstly, un upper digestive endoscopy is performed with a conventional gastroscope. A guidewire is passed through the malignant lesion causing the gastric outlet obstruction. Once the guidewire is located in the distal duodenum/proximal jejunum, a nasobiliary drain (Nasal Biliary Drainage Sets, Cook medical, Indiana) is advanced over the guidewire until its distal end is placed in the distal duodenum/jejunum. At this point the gastroscope is substituted by a therapeutic echoendoscope. With the echoendoscope in place, the target bowel loop is filled with saline combined with methilene blue and radiopaque contrast. The echoendoscope is used to identify the target bowel loop. AFter identifying the target, a lumen apposing metal stent (Axios, Boston Scientific, Massachusetts) is deployed across the gastric and bowel using its electrocautery enhanced deployment device.

Post procedure: Oral liquid intake can be restarted 4h after the procedure in patients presenting no signs or symptoms suggesting any adverse event. Pacients with an adequate tolerance might be discharged.

Follow-up

Clinical telephone interviews by an experienced research nurse will be held via telephone calls 1 day, 7 days and 30 days after the procedure. Oral intake and adverse events will be assessed every visit. Thirty days after the procedure a second evaluation of the EORTC-QLQ-C30 will be performed.

STATISTICAL ANALYSIS

Categorical variables were reported as percentages. Normally distributed continuous variables were reported as the mean with the standard deviation values. Non-normally distributed continuous variables were reported as the median and interquartile range. The EORTC QLQ-C30 descriptive analysis was performed with a specifically programmed Stata command (10). Variables regarding the procedure step by step analysis will only undergo a descriptive analysis. Differences between the different outcomes of the EORTC-QLQ-C30 will be assessed using linear mixed models with fixed effects for baseline values, and interaction with oncological treatment. The statistical analysis will be performed using the Stata package (StataCorp. 2013, College Station, Texas).

Study Design

• Study Type: Observational [Patient Registry]
• Actual Enrollment: 66 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Target Follow-Up Duration: 1 Month
• Official Title: Serie de Casos Prospectiva de Gastroenteroanastomosis Guiada Por Ecoendoscopia Para la obstrucción al Vaciado gástrico en Neoplasias Avanzadas Mediante la técnica Del Drenaje Nasobiliar
• Actual Study Start Date: August 15, 2019
• Actual Primary Completion Date: May 12, 2021
• Actual Study Completion Date: May 12, 2021

Groups and Cohorts

Group/Cohort

Intervention/treatment

Group 1; Patients included will undergo an EUS-guided gastroenterostomy with a 15x10mm or a 20x10mm lumen apposing metal Stent (Axios, Boston Scientific, Mass).

Device: EUS-guided gastroenterostomy; Firstly, un upper digestive endoscopy is performed with a conventional gastroscope. A guidewire is passed through the malignant lesion causing the gastric outlet obstruction. Once the guidewire is located in the distal duodenum/proximal jejunum, a nasobiliary drain (Nasal Biliary Drainage Sets, Cook medical, Indiana) is advanced over the guidewire until its distal end is placed in the distal duodenum/jejunum. At this point the gastroscope is substituted by a therapeutic echoendoscope. With the echoendoscope in place, the target bowel loop is filled with saline combined with methilene blue and radiopaque contrast. The echoendoscope is used to identify the target bowel loop. AFter identifying the target, a lumen apposing metal stent (Axios, Boston Scientific, Massachusetts) is deployed across the gastric and bowel using its electrocautery enhanced deployment device.; Other Name: AXIOS™ Stent and Electrocautery Enhanced Delivery System (Boston Scientific, Mass)

Outcome Measures

Primary Outcome Measures :

1. Technical Success [ Time Frame: Day +1 ]
   An adequate stent placement across the GI walls, with one flange in the gastric cavity and the other in the small bowel lumen. It has to be confirmed either fluoroscopically or endoscopically.
2. Early Clinical Success [ Time Frame: Day +7 ]
   Defined as a GOOSS >=2.
3. Clinical Success [ Time Frame: Day +30 ]
   Defined as a GOOSS >=2.

Secondary Outcome Measures :

1. Baseline Gastric outlet obstruction score system (GOOSS) [ Time Frame: Baseline ]
   The GOOSS is a previously defined classification of Gastric outlet obstruction which incudes 4 categories (0-Nil Per Os; 1 liquids only; 2 soft diet; 3 low residue or full diet)
2. Early Gastric outlet obstruction score system (GOOSS) [ Time Frame: day +7 ]
   The GOOSS is a previously defined classification of Gastric outlet obstruction which incudes 4 categories (0-Nil Per Os; 1 liquids only; 2 soft diet; 3 low residue or full diet)
3. Final Gastric outlet obstruction score system (GOOSS) [ Time Frame: day +30 ]
   The GOOSS is a previously defined classification of Gastric outlet obstruction which incudes 4 categories (0-Nil Per Os; 1 liquids only; 2 soft diet; 3 low residue or full diet)
4. Baseline European Organisation for Research and Treatment of Cancer QoL Questionnaire Core 30 (EORTC-QLQ-C30) [ Time Frame: Baseline ]
   The EORTC-QLQ-C30 is a validated questionnaire (with validated translations in Spanish), which includes 30 items covering a global health status scale, five functional scales and ten symptom scales
5. Final European Organisation for Research and Treatment of Cancer QoL Questionnaire Core 30 (EORTC-QLQ-C30) [ Time Frame: Baseline, day+30 ]
   The EORTC-QLQ-C30 is a validated questionnaire (with validated translations in Spanish), which includes 30 items covering a global health status scale, five functional scales and ten symptom scales
6. Number of Participants With intraprocedure Treatment-Related Adverse Events as Assessed by the ASGE classification [ Time Frame: day+1, ]
   The ASGE classification is a tool developed to describe and assess the severity of endoscopy related adverse events.
7. Number of Participants With Early Treatment-Related Adverse Events as Assessed by the ASGE classification [ Time Frame: day+7 ]
   The ASGE classification is a tool developed to describe and assess the severity of endoscopy related adverse events.
8. Number of Participants With Delayed Treatment-Related Adverse Events as Assessed by the ASGE classification [ Time Frame: day+30 ]
   The ASGE classification is a tool developed to describe and assess the severity of endoscopy related adverse events.
9. Recurrent GOO [ Time Frame: Day +30 ]
   In patients achieving clinical success in day +7, recurrent GOO is defined as the development of nausea and vomiting and/or a GOOSS<2.
10. Target bowel loop diameter (mm) [ Time Frame: Procedure ]
    Diameter measured with the EUS of the dilated bowel loop. It should be measured just before placing the stent
11. Total volume infused (ml) [ Time Frame: Procedure ]
    Volume of saline, methilene blue solution or radiopaque contrast solution instiled to dilate the target bowel loop
12. Number of patients undergoing balloon dilation [ Time Frame: Procedure ]
    After deploying the stent, it might be dilated with a controlled radial expansion balloon dilator
13. Type of fluid employed [ Time Frame: Procedure ]
    Three different fluids can be used to dilate the target bowel loop, saline, methilene blue diluted in saline or radiopaque contrast diluted in saline

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

All consecutive patients over 18 years of age submitted to any of the participanting center's endoscopy units to receive a nasobiliary drain assisted EUS-GE for unresectable malignant GOO are eligible to participate in this study.

Patients with a previous gastroduodenal surgery, a previous endoscopic or surgical treatment for GOO, a simultaneous malignant biliary obstruction or unable to understand the questionnaires will be excluded.

Criteria

Inclusion Criteria:

• Patients over 18 years of age
• unresectable malignant gastric outlet obstruction
• Undergoing placement of nasobiliary drain assisted EUS-GE

Exclusion Criteria:

• Previous gastroduodenal surgery
• Previous endoscopic or surgical treatment for gastric outlet obstruction
• Simultaneous biliary obstruction (malignant or benign) requiring endoscopic treatment
• Simultaneous upper digestive tract disease requiring endoscopic treatment in the same procedure
• Unable to understand the questionnaires
• Distal bowel obstruction
• Ascites grade 2 or superior
• Uncorrectable coagulation disorders (INR>1,5) or severe thrombocytopenia (<50000 platelets/mm3).
• Active, symptomatic SARS-CoV-2 infection

Contacts and Locations

Locations

India

Christian Medical College

Vellore, India

Spain

Clinica Universidad de Navarra

Pamplona, Navarra, Spain, 31008

Complejo Hospitalario de Navarra

Pamplona, Navarra, Spain, 31008

Hospital General Universitario de Alicante

Alicante, Spain, 03010

Hospital Universitario Río Hortega

Valladolid, Spain, 47014

Sponsors and Collaborators

Hospital del Río Hortega

Hospital General Universitario de Alicante

Clinica Universidad de Navarra, Universidad de Navarra

Complejo Hospitalario de Navarra

Christian Medical College, Vellore, India

Investigators

• Principal Investigator: Carlos de la Serna Higuera, MD; Hospital del Río Hortega

  Study Documents (Full-Text)

Documents provided by Francisco Javier Garcia Alonso, Hospital del Río Hortega:

Study Protocol and Statistical Analysis Plan  [PDF] August 21, 2019

More Information

• Responsible Party: Francisco Javier Garcia Alonso, Md PhD, Hospital del Río Hortega
• ClinicalTrials.gov Identifier: NCT04660695
• Other Study ID Numbers: PI152-19
• First Posted: December 9, 2020
• Last Update Posted: May 14, 2021
• Last Verified: May 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: After the study is completed a csv including all study data can be submitted to a repository or made available to applying investigators.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Additional relevant MeSH terms:

Gastric Outlet Obstruction; Pyloric Stenosis; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases