Treatment of Suspected Cholelithiasis With Nitroglycerin

Sponsor

United States Naval Medical Center, San Diego (U.S. Fed)

Overall Status

Unknown status

CT.gov ID

NCT01715220

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

ABSTRACT: Sublingual nitroglycerin has been advocated for the treatment of acute pain from suspected symptomatic cholelithiasis. There is, however, no clinical studies that validate its use. This study is designed to evaluate the efficacy of nitroglycerine in relieving acute pain of suspected biliary tract origin.

Nitroglycerin is a potent smooth muscle relaxant used for biliary tract dilation during ERCP, (Chelly, J) and has been recommended for treatment of biliary colic based on anecdotal experience and small case reports. Nitroglycerin effect is a result of the nitric oxide component of the medication which acts as a smooth muscle relaxant in vascular, bronchial, esophageal and biliary smooth muscles. [McGowan(1936), Chelly (1979),Toyoyama (2001)] The typical dose of nitroglycerin is 0.4 mg given sublingually in pill form or, more recently, in a metered spray form. In a case series reported by Hassel (1993), positive response times ranged from 20 to 60 seconds with duration of action of two to twelve hours. Sublingual nitroglycerin is most commonly used for treatment of chest pain related to insufficient cardiac perfusion. It has also been noted to relieve the pain of esophageal spasms. Nitroglycerin has an excellent safety profile if used in patients with adequate pretreatment blood pressures. [Newberry (2005), Nitroglycerine (2011), Nitro (2011), Wolters (2009)] This study proposes to compare sublingual 0.4 mg doses of nitroglycerin to placebo for the initial treatment of acute pain from suspected symptomatic cholelithiasis

Condition or Disease	Intervention/Treatment	Phase
COLIC BILIARY TRACT DISEASES	Drug: sublingual nitroglycerine	Phase 2

Detailed Description

General Approach: This study proposes to compare sublingual 0.4 mg doses of nitroglycerin to placebo for initial treatment for acute pain from suspected symptomatic cholelithiasis. Patients with right upper quadrant abdominal pain of less than 24 hour duration between ages 18 and 60 years of age will be offered treatment with sublingual nitroglycerin or placebo. Patients with obstructive hypertrophic cardiomyopathy, pronounced hypovolemia, STEMI or presumed cardiac chest pain, inferior myocardial infarction with right ventricular involvement, raised intracranial pressure, cardiac tamponade, and patients taking certain drugs for erectile dysfunction (phosphodiesterase inhibitors), pregnancy, or with a known allergy to nitroglycerin will be excluded from the study.

Methods: A convenience sample of patients presenting to the Emergency Department will be randomized to receive either sublingual 0.4 mg doses of nitroglycerin or placebo. Pain prior to and at two minutes and five minutes after medication administration will be assessed using a visual analog scale. The medication will be either a 0.4 mg dose of nitroglycerin or a placebo. If pain is not completely relieved within five minutes, a second dose will be administered after blood pressure assessment. If the pain is not completely relieved after an additional two minute and five minute assessment or the pain returns, it will be treated in the standard manner at the discretion of the treating Emergency Physician. Ancillary studies and other treatments will be at the discretion of the treating physician. The 0.4mg dose of nitro has been proven to be a safe and well tolerated dose when administered to our patient population in treatment of acute coronary syndrome or suspected angina. Our attending, resident, and nursing staff are very familiar with this dose, the potential side effects of the medication, and its administration procedure. Therefore, we believe that 0.4mg will be a optimal starting dose for enrollees in our study.
Retrovirology Research: None
Investigational Drugs/Devices/Biologics Research: None
Statistical Analysis: Demographic information, patient characteristics, assignment to experimental group, and visual analog pain scale data will be entered into a spreadsheet . Pain will be recorded per patients at 5 time points: 0, 2, 5, 7, and 10 minutes. Descriptive statistics will be presented in tables and graphs. Pain scale results will be analyzed by a two-way (2x5) repeated measures analysis of variance with interaction and post hoc multiple comparisons. The primary time pair to be tested will be the difference between treatment and placebo groups in pain reduction from 0 to 2 minutes. The planned sample size is 62, with 31 in the placebo group and 31 in the nitro group. The sample size was calculated with the aid of Dr Riffenburgh. He agrees with sample size suggested above.
Military Relevance / Operational Use, if any: Sublingual nitroglycerin is a standard AMAL list item for independent providers in most field and operational settings. Relief of biliary colic can significantly reduce the number of urgent medical evacuations for right upper quadrant pain. There is also no mental status degradation with the use of nitroglycerin, unlike the opioids commonly used to treat biliary colic.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

62 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

Treatment of Suspected Cholelithiasis With Nitroglycerin: a Randomized, Prospective Double-blind Trial

Study Start Date :

Oct 1, 2014

Anticipated Primary Completion Date :

Dec 1, 2018

Anticipated Study Completion Date :

Mar 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Sublingual nitroglycerine Sublingual nitroglycerine followed by pain assessment and if necessary second dose of sublingual nitroglycerine	Drug: sublingual nitroglycerine A convenience sample of patients presenting to the Emergency Department will be randomized to receive either sublingual 0.4 mg doses of nitroglycerin or placebo. Pain prior to and at two minutes and five minutes after medication administration will be assessed using a visual analog scale. The medication will be either a 0.4 mg dose of nitroglycerin or a placebo. If pain is not completely relieved within five minutes, a second dose will be administered after blood pressure assessment. If the pain is not completely relieved after an additional two minute and five minute assessment or the pain returns, it will be treated in the standard manner at the discretion of the treating Emergency Physician Other Names: Nitrolingual
Placebo Comparator: placebo sublingual placebo followed by pain assessment and if necessary second dose of sublingual placebo	Drug: sublingual nitroglycerine A convenience sample of patients presenting to the Emergency Department will be randomized to receive either sublingual 0.4 mg doses of nitroglycerin or placebo. Pain prior to and at two minutes and five minutes after medication administration will be assessed using a visual analog scale. The medication will be either a 0.4 mg dose of nitroglycerin or a placebo. If pain is not completely relieved within five minutes, a second dose will be administered after blood pressure assessment. If the pain is not completely relieved after an additional two minute and five minute assessment or the pain returns, it will be treated in the standard manner at the discretion of the treating Emergency Physician Other Names: Nitrolingual

Arm

Intervention/Treatment

Active Comparator: Sublingual nitroglycerine

Sublingual nitroglycerine followed by pain assessment and if necessary second dose of sublingual nitroglycerine

Drug: sublingual nitroglycerine

A convenience sample of patients presenting to the Emergency Department will be randomized to receive either sublingual 0.4 mg doses of nitroglycerin or placebo. Pain prior to and at two minutes and five minutes after medication administration will be assessed using a visual analog scale. The medication will be either a 0.4 mg dose of nitroglycerin or a placebo. If pain is not completely relieved within five minutes, a second dose will be administered after blood pressure assessment. If the pain is not completely relieved after an additional two minute and five minute assessment or the pain returns, it will be treated in the standard manner at the discretion of the treating Emergency Physician

Other Names:

Nitrolingual

Placebo Comparator: placebo

sublingual placebo followed by pain assessment and if necessary second dose of sublingual placebo

Drug: sublingual nitroglycerine

Other Names:

Nitrolingual

Outcome Measures

Primary Outcome Measures

pain relief on visual analog scale [two and five minutes]
pain relief assesement at two and five minutes after medication or placebo with standard treatment if inadequate pain relief.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria: Patients with right upper quadrant abdominal pain of less than 24 hours' duration between ages 18 and 60 years of age will be offered treatment with sublingual nitroglycerin or placebo.

Exclusion Criteria: Patients with obstructive hypertrophic cardiomyopathy, pronounced hypovolemia, alcohol use in the last 8 hours, clinical intoxication, STEMI or presumed cardiac chest pain, inferior myocardial infarction with right ventricular involvement, raised intracranial pressure, cardiac tamponade and patients taking certain drugs for erectile dysfunction (phosphodiesterase inhibitors), pregnancy or with a known allergy to nitroglycerin will be excluded from the study. Patients unable to give consent will be excluded.