Comparative Efficacy of Water & Indigo Carmine vs. Water or Air Method on Adenoma Detection Rate (ADR) - a Randomized Controlled Trial (RCT)

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT01607255
• Collaborator: (none)
• Enrollment: 480
• Location: 1
• Arms: 3
• Actual Duration (Months): 52.5
• Patients Per Site Per Month: 9.1

Study Details

Study Description

Brief Summary

Adenoma detection rate (ADR) is a quality indicator of colonoscopy performed for colorectal cancer screening. Population studies have shown that traditional air colonoscopy fails to eliminate post screening colonoscopy cancers or cancer mortality in the proximal colon. The investigators aim to establish the superior effectiveness of combining chromoendoscopy with the water exchange method in detecting more proximal diminutive adenomas during screening colonoscopy in sedated Veterans. An improved adenoma detection rate associated with optical colonoscopy will minimize the risk of missed lesions. The improvement may translate into a remedy for the limitations of screening colonoscopy in the proximal colon, e.g. a higher adenoma detection rate may minimize the burden of post screening colonoscopy interval colorectal cancers among the veteran population.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Neoplasms	Drug: Indigo carmine; Procedure: water (exchange) method; Procedure: water (exchange) plus dye method; Procedure: air method	Phase 4

Detailed Description

1. Design: Prospective, single center, patient blinded, randomized controlled trial

2. Methods: Colonoscopy with traditional air insufflation, water exchange or water exchange plus indigocarmine to aid insertion of colonoscope; split dose bowel preparation; all patients will receive sedation; assessment of serum electrolytes level before and after colonoscopy

3. Control method: Traditional air insufflation method.

4. Study methods:

• Water exchange method.

• Water method combined with chromoendoscopy (0.008% indigo carmine).

1. Population to be studied Veterans between age 50 and 75 referred for first time screening colonoscopy

2. Unit(s) of analysis

3. Primary outcome: overall adenoma detection rate.

4. Secondary outcomes: patient demographic variable and procedure related measures.

5. Sampling strategy: all Veterans referred for screening colonoscopy will be offered enrollment in the study.

6. Sample size calculation. A total of 480 subjects will be recruited and randomized with 160 in each group.

7. Subject recruitment: patients referred for screening colonoscopy come from three sources.

8. Description of base population and groups to be studied and method of randomization.

Veterans between age 50 and 75 referred for first time screening colonoscopy. After informed consent, assignment to control or study arm based on computer generated random number codes stored in pre-arranged opaque envelopes.

Study Design

• Study Type: Interventional
• Actual Enrollment: 480 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Comparative Efficacy of Water & Indigo Carmine vs Water or Air Method
• Actual Study Start Date: May 16, 2013
• Actual Primary Completion Date: Jun 30, 2017
• Actual Study Completion Date: Sep 30, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: water (exchange) method Residual pocket of air will be suctioned. Water is infused using a peristaltic pump to facilitate scope advancement until the cecum is reached. Dirty water will be suctioned and clean water is infused. Air will not be insufflated until the cecum is reached. Residual water is suctioned and air insufflated on scope withdrawal to facilitate biopsy and removal of lesions.	Procedure: water (exchange) method; Residual pocket of air will be suctioned. Water is infused using a peristaltic pump to facilitate scope advancement until the cecum is reached. Dirty water will be suctioned and clean water is infused. Air will not be insufflated until the cecum is reached. Residual water is suctioned and air insufflated on scope withdrawal to facilitate biopsy and removal of lesions.
Experimental: water (exchange) plus dye method Residual pocket of air will be suctioned. Water with 0.008% indigocarmine is infused using a peristaltic pump to facilitate scope advancement until the cecum is reached. Dirty water will be suctioned and clean water is infused. Air will not be insufflated until the cecum is reached. Residual water is suctioned and air insufflated on scope withdrawal to facilitate biopsy and removal of lesions	Drug: Indigo carmine; 0.008% indigo carmine in water is used as a surface contrast agent to enhance visualization of diminutive polyps (adenoma) during screening colonoscopy; Procedure: water (exchange) plus dye method; Residual pocket of air will be suctioned. Water with 0.008% indigocarmine is infused using a peristaltic pump to facilitate scope advancement until the cecum is reached. Dirty water will be suctioned and clean water is infused. Air will not be insufflated until the cecum is reached. Residual water is suctioned and air insufflated on scope withdrawal to facilitate biopsy and removal of lesions
Active Comparator: air method The colonoscope is inserted gently and advanced slowly using minimal air insufflation, if necessary, the assistant will provide abdominal compression or the patient's position will be changed to facilitate scope passage. The scope is inserted until the cecum is reached. Air is insufflated on scope withdrawal for visualization and water irrigation is used to remove any adherent feces covering the mucosa. Biopsy or polypectomy is performed where indicated.	Procedure: air method; The colonoscope is inserted gently and advanced slowly using minimal air insufflation, if necessary, the assistant will provide abdominal compression or the patient's position will be changed to facilitate scope passage. The scope is inserted until the cecum is reached. Air is insufflated on scope withdrawal for visualization and water irrigation is used to remove any adherent feces covering the mucosa. Biopsy or polypectomy is performed where indicated.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Detected Proximal Diminutive (<10 mm) Adenoma Detection Rate [36 months]

   Proximal diminutive adenoma detection rate (ADR) in screening colonoscopy performed with the unusual air method, versus the water (exchange) method and with dye added to the water (exchange) method

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• asymptomatic Veterans scheduled for first time screening colonoscopy and agree to be randomized will be enrolled.

Exclusion Criteria:

• patients who decline to be randomized, non screening cases.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Northern California Health Care System, Mather, CA	Sacramento	California	United States	95655

Sponsors and Collaborators

• VA Office of Research and Development

Investigators

• Principal Investigator: Joseph W. Leung, MD, VA Northern California Health Care System, Mather, CA

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 29, 2018

More Information

Publications

• Leung FW, Leung JW, Siao-Salera RM, Mann SK, Jackson G. The water method significantly enhances detection of diminutive lesions (adenoma and hyperplastic polyp combined) in the proximal colon in screening colonoscopy - data derived from two RCT in US veterans. J Interv Gastroenterol. 2011 Apr;1(2):48-52.
• Leung FW, Pan Y, Mann SK, Leung JW, Siao-Salera RM, Jackson G. The water exchange method and difficult colonoscopy. J Interv Gastroenterol. 2012 Jul;2(3):103-105. Epub 2012 Jul 1.
• Leung J, Mann S, Siao-Salera R, Ngo C, McCreery R, Canete W, Leung F. Indigocarmine added to the water exchange method enhances adenoma detection - a RCT. J Interv Gastroenterol. 2012 Jul;2(3):106-111. Epub 2012 Jul 1.
• Leung J, Mann S, Siao-Salera R, Ransibrahmanakul K, Lim B, Canete W, Samson L, Gutierrez R, Leung FW. A randomized, controlled trial to confirm the beneficial effects of the water method on U.S. veterans undergoing colonoscopy with the option of on-demand sedation. Gastrointest Endosc. 2011 Jan;73(1):103-10. doi: 10.1016/j.gie.2010.09.020.
• Leung JW, Do LD, Siao-Salera RM, Ngo C, Parikh DA, Mann SK, Leung FW. Retrospective analysis showing the water method increased adenoma detection rate - a hypothesis generating observation. J Interv Gastroenterol. 2011 Jan;1(1):3-7.
• Leung JW, Mann SK, Siao-Salera R, Ransibrahmanakul K, Lim B, Cabrera H, Canete W, Barredo P, Gutierrez R, Leung FW. A randomized, controlled comparison of warm water infusion in lieu of air insufflation versus air insufflation for aiding colonoscopy insertion in sedated patients undergoing colorectal cancer screening and surveillance. Gastrointest Endosc. 2009 Sep;70(3):505-10. doi: 10.1016/j.gie.2008.12.253. Epub 2009 Jun 24.
• Leung JW, Ransibrahmanakul K, Toomsen L, Mann SK, Siao-Salera R, Leung FW. The water method combined with chromoendoscopy enhances adenoma detection. J Interv Gastroenterol. 2011 Apr;1(2):53-58.
• Leung JW, Siao-Salera R, Abramyan O, Mann SK, Ward G, Yen A, Gutierrez R, Leung FW. Impact of water exchange colonoscopy on serum sodium and potassium levels: an observational study. Dig Dis Sci. 2014 Mar;59(3):653-7. doi: 10.1007/s10620-013-2934-0. Epub 2013 Nov 20.
• Leung JW, Thai A, Yen A, Ward G, Abramyan O, Lee J, Smith B, Leung F. Magnetic endoscope imaging (ScopeGuide) elucidates the mechanism of action of the pain-alleviating impact of water exchange colonoscopy - attenuation of loop formation. J Interv Gastroenterol. 2012 Jul;2(3):142-146. Epub 2012 Jul 1.
• Ngo C, Leung JW, Mann SK, Terrado C, Bowlus C, Ingram D, Leung FW. Interim report of a randomized cross-over study comparing clinical performance of novice trainee endoscopists using conventional air insufflation versus warm water infusion colonoscopy. J Interv Gastroenterol. 2012 Jul;2(3):135-139. Epub 2012 Jul 1.
• Yen AW, Leung JW, Leung FW. A new method for screening and surveillance colonoscopy: Combined water-exchange and cap-assisted colonoscopy. J Interv Gastroenterol. 2012 Jul;2(3):114-119. Epub 2012 Jul 1.
• Yen AW, Leung JW, Leung FW. A novel method with significant impact on adenoma detection: combined water-exchange and cap-assisted colonoscopy. Gastrointest Endosc. 2013 Jun;77(6):944-8. doi: 10.1016/j.gie.2013.01.011. Epub 2013 Mar 6.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT01607255
• Other Study ID Numbers: CLIN-10-11S
• First Posted: May 30, 2012
• Last Update Posted: Jan 15, 2019
• Last Verified: Jan 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by VA Office of Research and Development: adenoma detection; screening colonoscopy; water exchange method; chromoendoscopy
• Additional relevant MeSH terms: Colorectal Neoplasms

Study Results

Participant Flow

Arm/Group Title	Water (Exchange) Method	Water (Exchange) Plus Dye Method	Air Method
Arm/Group Description	Residual pocket of air will be suctioned. Water is infused using a peristaltic pump to facilitate scope advancement until the cecum is reached. Dirty water will be suctioned and clean water is infused. Air will not be insufflated until the cecum is reached. Residual water is suctioned and air insufflated on scope withdrawal to facilitate biopsy and removal of lesions. water (exchange) method: Residual pocket of air will be suctioned. Water is infused using a peristaltic pump to facilitate scope advancement until the cecum is reached. Dirty water will be suctioned and clean water is infused. Air will not be insufflated until the cecum is reached. Residual water is suctioned and air insufflated on scope withdrawal to facilitate biopsy and removal of lesions.	Residual pocket of air will be suctioned. Water with 0.008% indigocarmine is infused using a peristaltic pump to facilitate scope advancement until the cecum is reached. Dirty water will be suctioned and clean water is infused. Air will not be insufflated until the cecum is reached. Residual water is suctioned and air insufflated on scope withdrawal to facilitate biopsy and removal of lesions Indigo carmine: 0.008% indigo carmine in water is used as a surface contrast agent to enhance visualization of diminutive polyps (adenoma) during screening colonoscopy water (exchange) plus dye method: Residual pocket of air will be suctioned. Water with 0.008% indigocarmine is infused using a peristaltic pump to facilitate scope advancement until the cecum is reached. Dirty water will be suctioned and clean water is infused. Air will not be insufflated until the cecum is reached. Residual water is suctioned and air insufflated on scope withdrawal to facilitate biopsy and removal of lesions	The colonoscope is inserted gently and advanced slowly using minimal air insufflation, if necessary, the assistant will provide abdominal compression or the patient's position will be changed to facilitate scope passage. The scope is inserted until the cecum is reached. Air is insufflated on scope withdrawal for visualization and water irrigation is used to remove any adherent feces covering the mucosa. Biopsy or polypectomy is performed where indicated. air method: The colonoscope is inserted gently and advanced slowly using minimal air insufflation, if necessary, the assistant will provide abdominal compression or the patient's position will be changed to facilitate scope passage. The scope is inserted until the cecum is reached. Air is insufflated on scope withdrawal for visualization and water irrigation is used to remove any adherent feces covering the mucosa. Biopsy or polypectomy is performed where indicated.
Period Title: Overall Study
STARTED	161	160	159
COMPLETED	161	160	159
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Water (Exchange) Method	Water (Exchange) Plus Dye Method	Air Method	Total
Arm/Group Description	Residual pocket of air will be suctioned. Water is infused using a peristaltic pump to facilitate scope advancement until the cecum is reached. Dirty water will be suctioned and clean water is infused. Air will not be insufflated until the cecum is reached. Residual water is suctioned and air insufflated on scope withdrawal to facilitate biopsy and removal of lesions. water (exchange) method: Residual pocket of air will be suctioned. Water is infused using a peristaltic pump to facilitate scope advancement until the cecum is reached. Dirty water will be suctioned and clean water is infused. Air will not be insufflated until the cecum is reached. Residual water is suctioned and air insufflated on scope withdrawal to facilitate biopsy and removal of lesions.	Residual pocket of air will be suctioned. Water with 0.008% indigocarmine is infused using a peristaltic pump to facilitate scope advancement until the cecum is reached. Dirty water will be suctioned and clean water is infused. Air will not be insufflated until the cecum is reached. Residual water is suctioned and air insufflated on scope withdrawal to facilitate biopsy and removal of lesions Indigo carmine: 0.008% indigo carmine in water is used as a surface contrast agent to enhance visualization of diminutive polyps (adenoma) during screening colonoscopy water (exchange) plus dye method: Residual pocket of air will be suctioned. Water with 0.008% indigocarmine is infused using a peristaltic pump to facilitate scope advancement until the cecum is reached. Dirty water will be suctioned and clean water is infused. Air will not be insufflated until the cecum is reached. Residual water is suctioned and air insufflated on scope withdrawal to facilitate biopsy and removal of lesions	The colonoscope is inserted gently and advanced slowly using minimal air insufflation, if necessary, the assistant will provide abdominal compression or the patient's position will be changed to facilitate scope passage. The scope is inserted until the cecum is reached. Air is insufflated on scope withdrawal for visualization and water irrigation is used to remove any adherent feces covering the mucosa. Biopsy or polypectomy is performed where indicated. air method: The colonoscope is inserted gently and advanced slowly using minimal air insufflation, if necessary, the assistant will provide abdominal compression or the patient's position will be changed to facilitate scope passage. The scope is inserted until the cecum is reached. Air is insufflated on scope withdrawal for visualization and water irrigation is used to remove any adherent feces covering the mucosa. Biopsy or polypectomy is performed where indicated.	Total of all reporting groups
Overall Participants	161	160	159	480
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	102 63.4%	105 65.6%	106 66.7%	313 65.2%
>=65 years	59 36.6%	55 34.4%	53 33.3%	167 34.8%
Sex: Female, Male (Count of Participants)
Female	22 13.7%	19 11.9%	24 15.1%	65 13.5%
Male	139 86.3%	141 88.1%	135 84.9%	415 86.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	14 8.7%	12 7.5%	11 6.9%	37 7.7%
Not Hispanic or Latino	146 90.7%	147 91.9%	148 93.1%	441 91.9%
Unknown or Not Reported	1 0.6%	1 0.6%	0 0%	2 0.4%
Region of Enrollment (Count of Participants)
United States	161 100%	160 100%	159 100%	480 100%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29.6 (4.1)	29.2 (4.3)	29.4 (4.3)	29.4 (4.2)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Detected Proximal Diminutive (<10 mm) Adenoma Detection Rate
Description	Proximal diminutive adenoma detection rate (ADR) in screening colonoscopy performed with the unusual air method, versus the water (exchange) method and with dye added to the water (exchange) method
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Water (Exchange) Method	Water (Exchange) Plus Dye Method	Air Method
Arm/Group Description	Residual pocket of air will be suctioned. Water is infused using a peristaltic pump to facilitate scope advancement until the cecum is reached. Dirty water will be suctioned and clean water is infused. Air will not be insufflated until the cecum is reached. Residual water is suctioned and air insufflated on scope withdrawal to facilitate biopsy and removal of lesions. water (exchange) method: Residual pocket of air will be suctioned. Water is infused using a peristaltic pump to facilitate scope advancement until the cecum is reached. Dirty water will be suctioned and clean water is infused. Air will not be insufflated until the cecum is reached. Residual water is suctioned and air insufflated on scope withdrawal to facilitate biopsy and removal of lesions.	Residual pocket of air will be suctioned. Water with 0.008% indigocarmine is infused using a peristaltic pump to facilitate scope advancement until the cecum is reached. Dirty water will be suctioned and clean water is infused. Air will not be insufflated until the cecum is reached. Residual water is suctioned and air insufflated on scope withdrawal to facilitate biopsy and removal of lesions Indigo carmine: 0.008% indigo carmine in water is used as a surface contrast agent to enhance visualization of diminutive polyps (adenoma) during screening colonoscopy water (exchange) plus dye method: Residual pocket of air will be suctioned. Water with 0.008% indigocarmine is infused using a peristaltic pump to facilitate scope advancement until the cecum is reached. Dirty water will be suctioned and clean water is infused. Air will not be insufflated until the cecum is reached. Residual water is suctioned and air insufflated on scope withdrawal to facilitate biopsy and removal of lesions	The colonoscope is inserted gently and advanced slowly using minimal air insufflation, if necessary, the assistant will provide abdominal compression or the patient's position will be changed to facilitate scope passage. The scope is inserted until the cecum is reached. Air is insufflated on scope withdrawal for visualization and water irrigation is used to remove any adherent feces covering the mucosa. Biopsy or polypectomy is performed where indicated. air method: The colonoscope is inserted gently and advanced slowly using minimal air insufflation, if necessary, the assistant will provide abdominal compression or the patient's position will be changed to facilitate scope passage. The scope is inserted until the cecum is reached. Air is insufflated on scope withdrawal for visualization and water irrigation is used to remove any adherent feces covering the mucosa. Biopsy or polypectomy is performed where indicated.
Measure Participants	161	160	159
Proximal ADR	86 53.4%	89 55.6%	83 52.2%
Serrated Lesion	38 23.6%	42 26.3%	18 11.3%

Adverse Events

Time Frame	Immediate adverse event data were collected within 7 days and long-term complication data were collected at 30 days.
Arm/Group Title	Water (Exchange) Method		Water (Exchange) Plus Dye Method		Air Method
Arm/Group Description	Residual pocket of air will be suctioned. Water is infused using a peristaltic pump to facilitate scope advancement until the cecum is reached. Dirty water will be suctioned and clean water is infused. Air will not be insufflated until the cecum is reached. Residual water is suctioned and air insufflated on scope withdrawal to facilitate biopsy and removal of lesions. water (exchange) method: Residual pocket of air will be suctioned. Water is infused using a peristaltic pump to facilitate scope advancement until the cecum is reached. Dirty water will be suctioned and clean water is infused. Air will not be insufflated until the cecum is reached. Residual water is suctioned and air insufflated on scope withdrawal to facilitate biopsy and removal of lesions.		Residual pocket of air will be suctioned. Water with 0.008% indigocarmine is infused using a peristaltic pump to facilitate scope advancement until the cecum is reached. Dirty water will be suctioned and clean water is infused. Air will not be insufflated until the cecum is reached. Residual water is suctioned and air insufflated on scope withdrawal to facilitate biopsy and removal of lesions Indigo carmine: 0.008% indigo carmine in water is used as a surface contrast agent to enhance visualization of diminutive polyps (adenoma) during screening colonoscopy water (exchange) plus dye method: Residual pocket of air will be suctioned. Water with 0.008% indigocarmine is infused using a peristaltic pump to facilitate scope advancement until the cecum is reached. Dirty water will be suctioned and clean water is infused. Air will not be insufflated until the cecum is reached. Residual water is suctioned and air insufflated on scope withdrawal to facilitate biopsy and removal of lesions		The colonoscope is inserted gently and advanced slowly using minimal air insufflation, if necessary, the assistant will provide abdominal compression or the patient's position will be changed to facilitate scope passage. The scope is inserted until the cecum is reached. Air is insufflated on scope withdrawal for visualization and water irrigation is used to remove any adherent feces covering the mucosa. Biopsy or polypectomy is performed where indicated. air method: The colonoscope is inserted gently and advanced slowly using minimal air insufflation, if necessary, the assistant will provide abdominal compression or the patient's position will be changed to facilitate scope passage. The scope is inserted until the cecum is reached. Air is insufflated on scope withdrawal for visualization and water irrigation is used to remove any adherent feces covering the mucosa. Biopsy or polypectomy is performed where indicated.
All Cause Mortality
	Water (Exchange) Method		Water (Exchange) Plus Dye Method		Air Method
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/161 (0%)		0/160 (0%)		0/159 (0%)
Serious Adverse Events
	Water (Exchange) Method		Water (Exchange) Plus Dye Method		Air Method
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/161 (2.5%)		3/160 (1.9%)		1/159 (0.6%)
Cardiac disorders
cardiovascular event	0/161 (0%)	0	1/160 (0.6%)	1	0/159 (0%)	0
Gastrointestinal disorders
post polypectomy abdominal pain	3/161 (1.9%)	3	1/160 (0.6%)	1	1/159 (0.6%)	1
post procedural bleeding	1/161 (0.6%)	1	1/160 (0.6%)	1	0/159 (0%)	0
Other (Not Including Serious) Adverse Events
	Water (Exchange) Method		Water (Exchange) Plus Dye Method		Air Method
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/161 (0%)		0/160 (0%)		0/159 (0%)

Limitations/Caveats

The limitations and caveat of this clinical study are: single center, single blinded (patients) study, single operator, and Veteran patients.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.