Ignite Creation Date:
2024-05-06 @ 6:50 PM
Last Modification Date:
2024-10-26 @ 2:55 PM
Study NCT ID:
NCT05801055
Status:
NOT_YET_RECRUITING
Last Update Posted:
2023-04-06
First Post:
2023-03-06
Brief Title:
A Study to Evaluate Endoscopic Visibility of Stomach After a Combination Drink of N-acetylcysteine and Simethicone
Sponsor:
Sanjay Gandhi Postgraduate Institute of Medical Sciences
Organization:
Sanjay Gandhi Postgraduate Institute of Medical Sciences
Study Overview
Official Title:
Improvement in Endoscopic Mucosal Visibility Using a Pre-procedure Combination Drink of N-acetylcysteine and Simethicone A Randomized Controlled Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2023-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Endoscopy is the diagnostic modality for most gastroduodenal diseases During endoscopy mucus and foam may actually interfere with the visibility of the stomach mucosa So the mixture of mucolytic N-acetyl cysteine and anti-foaming agents simethicone agents may disperse the bubbles and mucus in the stomach and enhance gastric visibility This unique combination drink given 20-30 minutes prior to endoscopy is absolutely safe There are previous studies from India which was retrospective study So we have planned to conduct this randomized controlled trial on this issue Adult patients undergoing diagnostic endoscopy will be randomized and one group 100 patients will be given the combination drink whereas another group 9100 patients will undergo an endoscopy after overnight fasting only as a placebo drink may actually hamper the endoscopic visibility Our primary outcome gastric visibility will be assessed using a standard visibility scoring system
Detailed Description:
Improvement in endoscopic mucosal visibility using a pre-procedure combination drink of N-acetylcysteine and simethicone A Randomized controlled trial
Introduction
Upper gastrointestinal endoscopy UGIE is one of the most frequently performed procedures for diagnosing and treating GI and liver-related disorders Pre-procedure preparation and reporting of adequate preparation is the standard of care for colonoscopies but there is not uniformity in preparation for UGIE Various studies have demonstrated that the incidence of missed diagnosis in endoscopies can be brought down by improving mucosal visibility Endoscopic mucosal visibility can be impaired by various factors like poor technique excessive mucus residual food inappropriate positioning and more importantly the presence of mucosal froth and bubbles in the GI tract Gastro-duodenal mucosa is lined by mucus comprising 95 water and 5 cross-linked glycoproteinGP which keeps mucus viscous and liquid With fasting GP content decreases making mucus more sticky Several mucolytic and anti-foaming agents including pronase simethicone and N acetyl-cysteineNAC have been tried for this purpose NAC is a derivative of the natural amino acid L-cysteine It breaks the disulfide bridges in high molecular weight glycoproteins Simethicone polydimethylsiloxane or dimethicone SiO2 is an anti-foaming surface-acting agent which acts by reducing the surface tension of air bubbles surface viscosity and hydrophobicity Simethicone is virtually non-toxic without any drug interaction or systemic toxicity Multiple studies have been conducted showing the safety and efficacy of simethicone NAC and their combination for improving endoscopic visibility These pre-medications are already used for improving endoscopic visibility to detect early esophageal and gastric cancer
Some studies from the western countries as well as the eastern world have highlighted the significant role of mucolytic and anti-foaming agents in improving mucosal visibility
Monrroy et al in 2017 conducted a double-blind randomized control trial in which 230 patients were divided into 5 groups 46 each ie no intervention group water 100 ml W group and interventional groups comprised of simethicone alone S simethicone plus NAC 500 mg S NAC500 and simethicone plus NAC1000 group The solution was ingested 20 minutes before the UGIE Gastric visibility was assessed in 4 segments using a pre-validated mucosal visibility scoring system based on a Likert scale and adequate visibility was defined as a score less than 7 In this study they found that premedication by SNAC500 and SNAC100 improved visibility whereas visibility was worst in the W group
Another study by Manfredi et al in 2020 which was a prospective endoscopist-blinded randomized study enrolled patients undergoing UGIE Patients were randomized to receive NACS solution vs placebo A pre-validated scoring system was used for the visibility assessment A total score of less than 5 was considered insufficient preparation The premeditated group had a significantly lower number of patients with a score 5 The need for water flush also occurred less in the premedicated group compared to the control group One retrospective investigator-blinded study was conducted in Sir Gangaram Hospital by Anikhindi et al in collaboration with Osaka International Cancer Institute Osaka Japan It was designed as a case-control study In this study group of patients who consumed 100 ml pre-endoscopy drink comprising of NAC simethicone group were compared with the fasting group Digital images were obtained from 6 pre-defined areas of the esophagus stomach and duodenum A blinded investigator scored them using a 3-point scale for mucosal visibility Mucosal visibility in the esophagus and stomach was significantly better in the NAC S group compared to the 100 ml water group There is no prospective data from India to validate the use of such pre-medications before routine UGIE Therefore we have designed a prospective randomized controlled trial to assess the improvement of mucosal visibility using a pre-endoscopic drink
Need of the study
Better visualization of the intestinal mucosa is important for diagnosing early changes of many benign lesions precancerous lesions like Barretts esophagus or early flat malignant lesions Most of the data about the role of NAC with simethicone are from Japan and the West so studying this in the Indian population is required
Aim of the study
1 To clarify the role of NAC S for better endoscopic mucosal visualization in the Indian population
Study Methodology
It will be a single-blind parallel-randomized controlled trial Randomization will be done using a table of random numbers Using a computer-generated sequence Allocation will be done through a sealed opaque envelope by a data entry operator to have allocation concealment not the endoscopist or investigator
The allocation ratio will be 11 between the study group and the control group The study will be registered in a clinical trial registry after Institutional ethics clearance before the start of the study
Study Centre Department of Gastroenterology Sanjay Gandhi Post Graduate Institute Lucknow
Duration of the study May - June 2023 Sample size calculation The sample size has been calculated using OpenEpi Version 3 CDC Atlanta The sample size was calculated taking the confidence limit CL of 99 power of the study of 95 and alpha error of 5 to detect a 25 difference in adequate visibility between the study and control group we got a minimum sample size of 174 87 each group Since we expect data loss and technical failure in 10-20 of patients we will include 100 patients in each group
Inclusion criteria
1 Consecutive patients presenting for ambulatory diagnostic endoscopy
2 Willing Informed consent
3 Age 18-75 years
Exclusion criteria
1 Patients undergoing therapeutic endoscopy
2 Patients undergoing emergency endoscopy
3 Deeply sedated anesthetized patients
4 Pregnant patients
5 Clinically suspected motility disorders gastroparesis achalasia
6 Patients with esophageal stricture
7 Patients with gastric outlet obstruction
Intervention All patients will undergo a routine UGIE with the following instructions
Upper GI endoscopy
Overnight fasting
Pharyngeal local anesthetic spray
Intervention Group
Premedication with 15mL emulsions of NAC 600mg Simethicone 150 mg diluted to 100 mL to be taken 10-30 mins prior to the procedure not later
Comparator
The Control group will not receive any placebo emulsion as it has been shown to worsen the visibility
Primary outcome
The difference in adequate visibility between the two groups Gastric total visibility score TVS 4-16 will be used as proposed by Monrroy et al 6 The scoring system has been pre-validated to assess gastric endoscopic mucosal visibility It will be calculated by assessment of mucosal visibility on a Likert scale of 1 to 4 in areas of the gastric antrum lower gastric body upper gastric body and fundus Figure 1
It will be calculated by a blinded investigator using electronic images captured during the endoscopy
A TVS 7 will be used to define adequate visibility AV
Secondary Outcome
1 Time is taken for the procedure scope-in-scope out
2 Adverse events
3 Gastric mucosal lesion yield
Statistical analysis All qualitative data will be presented as proportions and quantitative data will be expressed as mean standard deviation or median interquartile range as appropriate Adequate visibility gastric lesion yield and adverse events between the group will be compared using the Chi-squared test The time taken for the procedure between the two groups will be compared using the Mann-Whitney U test A power of 80 and an alpha error of 5 is permitted A p-value of 005 will be considered significant
Introduction
Upper gastrointestinal endoscopy UGIE is one of the most frequently performed procedures for diagnosing and treating GI and liver-related disorders Pre-procedure preparation and reporting of adequate preparation is the standard of care for colonoscopies but there is not uniformity in preparation for UGIE Various studies have demonstrated that the incidence of missed diagnosis in endoscopies can be brought down by improving mucosal visibility Endoscopic mucosal visibility can be impaired by various factors like poor technique excessive mucus residual food inappropriate positioning and more importantly the presence of mucosal froth and bubbles in the GI tract Gastro-duodenal mucosa is lined by mucus comprising 95 water and 5 cross-linked glycoproteinGP which keeps mucus viscous and liquid With fasting GP content decreases making mucus more sticky Several mucolytic and anti-foaming agents including pronase simethicone and N acetyl-cysteineNAC have been tried for this purpose NAC is a derivative of the natural amino acid L-cysteine It breaks the disulfide bridges in high molecular weight glycoproteins Simethicone polydimethylsiloxane or dimethicone SiO2 is an anti-foaming surface-acting agent which acts by reducing the surface tension of air bubbles surface viscosity and hydrophobicity Simethicone is virtually non-toxic without any drug interaction or systemic toxicity Multiple studies have been conducted showing the safety and efficacy of simethicone NAC and their combination for improving endoscopic visibility These pre-medications are already used for improving endoscopic visibility to detect early esophageal and gastric cancer
Some studies from the western countries as well as the eastern world have highlighted the significant role of mucolytic and anti-foaming agents in improving mucosal visibility
Monrroy et al in 2017 conducted a double-blind randomized control trial in which 230 patients were divided into 5 groups 46 each ie no intervention group water 100 ml W group and interventional groups comprised of simethicone alone S simethicone plus NAC 500 mg S NAC500 and simethicone plus NAC1000 group The solution was ingested 20 minutes before the UGIE Gastric visibility was assessed in 4 segments using a pre-validated mucosal visibility scoring system based on a Likert scale and adequate visibility was defined as a score less than 7 In this study they found that premedication by SNAC500 and SNAC100 improved visibility whereas visibility was worst in the W group
Another study by Manfredi et al in 2020 which was a prospective endoscopist-blinded randomized study enrolled patients undergoing UGIE Patients were randomized to receive NACS solution vs placebo A pre-validated scoring system was used for the visibility assessment A total score of less than 5 was considered insufficient preparation The premeditated group had a significantly lower number of patients with a score 5 The need for water flush also occurred less in the premedicated group compared to the control group One retrospective investigator-blinded study was conducted in Sir Gangaram Hospital by Anikhindi et al in collaboration with Osaka International Cancer Institute Osaka Japan It was designed as a case-control study In this study group of patients who consumed 100 ml pre-endoscopy drink comprising of NAC simethicone group were compared with the fasting group Digital images were obtained from 6 pre-defined areas of the esophagus stomach and duodenum A blinded investigator scored them using a 3-point scale for mucosal visibility Mucosal visibility in the esophagus and stomach was significantly better in the NAC S group compared to the 100 ml water group There is no prospective data from India to validate the use of such pre-medications before routine UGIE Therefore we have designed a prospective randomized controlled trial to assess the improvement of mucosal visibility using a pre-endoscopic drink
Need of the study
Better visualization of the intestinal mucosa is important for diagnosing early changes of many benign lesions precancerous lesions like Barretts esophagus or early flat malignant lesions Most of the data about the role of NAC with simethicone are from Japan and the West so studying this in the Indian population is required
Aim of the study
1 To clarify the role of NAC S for better endoscopic mucosal visualization in the Indian population
Study Methodology
It will be a single-blind parallel-randomized controlled trial Randomization will be done using a table of random numbers Using a computer-generated sequence Allocation will be done through a sealed opaque envelope by a data entry operator to have allocation concealment not the endoscopist or investigator
The allocation ratio will be 11 between the study group and the control group The study will be registered in a clinical trial registry after Institutional ethics clearance before the start of the study
Study Centre Department of Gastroenterology Sanjay Gandhi Post Graduate Institute Lucknow
Duration of the study May - June 2023 Sample size calculation The sample size has been calculated using OpenEpi Version 3 CDC Atlanta The sample size was calculated taking the confidence limit CL of 99 power of the study of 95 and alpha error of 5 to detect a 25 difference in adequate visibility between the study and control group we got a minimum sample size of 174 87 each group Since we expect data loss and technical failure in 10-20 of patients we will include 100 patients in each group
Inclusion criteria
1 Consecutive patients presenting for ambulatory diagnostic endoscopy
2 Willing Informed consent
3 Age 18-75 years
Exclusion criteria
1 Patients undergoing therapeutic endoscopy
2 Patients undergoing emergency endoscopy
3 Deeply sedated anesthetized patients
4 Pregnant patients
5 Clinically suspected motility disorders gastroparesis achalasia
6 Patients with esophageal stricture
7 Patients with gastric outlet obstruction
Intervention All patients will undergo a routine UGIE with the following instructions
Upper GI endoscopy
Overnight fasting
Pharyngeal local anesthetic spray
Intervention Group
Premedication with 15mL emulsions of NAC 600mg Simethicone 150 mg diluted to 100 mL to be taken 10-30 mins prior to the procedure not later
Comparator
The Control group will not receive any placebo emulsion as it has been shown to worsen the visibility
Primary outcome
The difference in adequate visibility between the two groups Gastric total visibility score TVS 4-16 will be used as proposed by Monrroy et al 6 The scoring system has been pre-validated to assess gastric endoscopic mucosal visibility It will be calculated by assessment of mucosal visibility on a Likert scale of 1 to 4 in areas of the gastric antrum lower gastric body upper gastric body and fundus Figure 1
It will be calculated by a blinded investigator using electronic images captured during the endoscopy
A TVS 7 will be used to define adequate visibility AV
Secondary Outcome
1 Time is taken for the procedure scope-in-scope out
2 Adverse events
3 Gastric mucosal lesion yield
Statistical analysis All qualitative data will be presented as proportions and quantitative data will be expressed as mean standard deviation or median interquartile range as appropriate Adequate visibility gastric lesion yield and adverse events between the group will be compared using the Chi-squared test The time taken for the procedure between the two groups will be compared using the Mann-Whitney U test A power of 80 and an alpha error of 5 is permitted A p-value of 005 will be considered significant
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None