Diphenhydramine as an Adjunctive Sedative in Patients on Chronic Opioids

NCT ID: NCT01967433

Last Updated: 2020-03-11

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-12-31

Study Completion Date

2018-07-31

Brief Summary

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To access the efficacy of adding diphenhydramine as adjunct to improve sedation and to reduce the amount of standard sedatives used during colonoscopy in patients on chronic opioids.

Detailed Description

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Specific Aims:

The primary aim of our study is to determine if addition of Diphenhydramine to Fentanyl and Midazolam will decrease the dose of Fentanyl and Midazolam used during colonoscopy in individuals on chronic opioids. Secondarily we will be looking at quality of sedation, duration of colonoscopy, time to reach cecum and adverse effects (hypoxia defined as O2 saturation less than 89% lasting for more than 30 seconds, hypotension defined as systolic BP less than 90 mmhg and use of reversal agents i.e Naloxone or Flumazenil).

Day of Procedure:

After consent is obtained the medical records of the patients will be reviewed and demographic information, co-morbidities, current medication will be extracted and recorded.

On the day of colonoscopy Alcohol use disorder inventory (AUDIT) will be used to screen for alcohol abuse. AUDIT was developed by World Health Organization and has been validated over a period of 2 decades. It consist of 10 questions, each question is scored 0-4 on the basis of subjects alcohol use. It takes about 2-4 minutes to complete. A score 10 or greater is highly specific or alcohol use.

Subjects will be checked in and prepared according to routine protocols of the VA medical center. Participants will be randomly assigned to receive either 50 mg of diphenhydramine or 10 ml of 0.9% sodium chloride. On the day of colonoscopy randomization will be performed by an independent investigator who is a pharmacist at VA medical center using the website http://www.randomization.com. She will also prepare and dispense medication. Each endoscopy team will consist of an attending gastroenterologist, gastroenterology fellow and two nurses. Medications will be administered by one of the nurses under the direct supervision of the physician.

At the start of procedure baseline vitals will be recorded as per our unit's policy. Research medication will be administered 3 minutes prior to administration of other medications. Neither the patient nor the medical staff including the endoscopist will be aware of the contents of the vial. Conscious sedation will be achieved using a combination of intravenous midazolam and fentanyl as standard sedative. Rarely, additional diphenhydramine will be given, on the basis of the judgment of the endoscopist. During the procedure vital signs including oxygen saturation will be monitored at 3-5 minute interval. Procedure related complications, including hypotension, desaturation and cardiac arrhythmia will be managed according to our endoscopy unit policy and protocols.

Following the procedure, the nurse and the fellow or the attending will individually rate the quality if sedation on a ten-point Likert scale. Qualitative assessment will also be made (Under-sedated, adequately sedated, or over-sedated).

Recovery time will be recorded.

Day Following the Colonoscopy Twenty-four hour discharge a follow up call will be made and the patients will be asked to evaluate the level of sedation on a 10-point scale (1, inadequate; 10 completely without discomfort); pain (1, no pain; 10 severe pain), and amnesia (10, no memory of the procedure; 1 complete memory).

Conditions

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Colonoscopy Adjunct Anesthesia Medication

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Diphenhydramine

Diphenhydramine 50 mg IV 3 minutes prior to administration of other sedatives

Group Type EXPERIMENTAL

Diphenhydramine

Intervention Type DRUG

Placebo

0.9% sodium chloride 10 ml IV 3 minuted prior to administration of other sedatives

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Interventions

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Diphenhydramine

Intervention Type DRUG

Placebo

Intervention Type DRUG

Other Intervention Names

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Benadryl Normal Saline 0.9% sodium chloride

Eligibility Criteria

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Inclusion Criteria

* Patients aged 18-64 years undergoing screening, surveillance, diagnostic and therapeutic colonoscopy
* Patient on chronic opioids defined as at least 5 mg of morphine or its equivalent at least 3 days per week for more than 3 months

Exclusion Criteria

* Inability to execute informed consent
* Allergy to Diphenhydramine, fentanyl or midazolam
* Known or suspected pregnancy
* Endoscopic procedure without sedation
* Patient scheduled to have other endoscopic procedures on the same day
* Prior alimentary tract surgery
* Severe cardiopulmonary disease (ASA IV)
* Monoamine Oxidase Inhibitors (MOI) use within 2 weeks of procedure
Minimum Eligible Age

18 Years

Maximum Eligible Age

64 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Oklahoma

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Salman Nusrat, MD

Role: STUDY_DIRECTOR

University of Oklahoma

Mohammad Madhoun, MD MS

Role: PRINCIPAL_INVESTIGATOR

Univeristy of Oklahoma Health Sciences Center

Locations

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Veterans Affairs Medical Center

Oklahoma City, Oklahoma, United States

Site Status

Countries

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United States

References

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Abraham NS, Fallone CA, Mayrand S, Huang J, Wieczorek P, Barkun AN. Sedation versus no sedation in the performance of diagnostic upper gastrointestinal endoscopy: a Canadian randomized controlled cost-outcome study. Am J Gastroenterol. 2004 Sep;99(9):1692-9. doi: 10.1111/j.1572-0241.2004.40157.x.

Reference Type BACKGROUND
PMID: 15330904 (View on PubMed)

Zubarik R, Ganguly E, Benway D, Ferrentino N, Moses P, Vecchio J. Procedure-related abdominal discomfort in patients undergoing colorectal cancer screening: a comparison of colonoscopy and flexible sigmoidoscopy. Am J Gastroenterol. 2002 Dec;97(12):3056-61. doi: 10.1111/j.1572-0241.2002.07101.x.

Reference Type BACKGROUND
PMID: 12492190 (View on PubMed)

Bergeron P, Enns J, Delima L, Dupuis JY, Wynands JE. Effects of routine premedication for cardiac catheterization on sedation, level of anxiety and arterial oxygen saturation. Can J Cardiol. 1995 Mar;11(3):201-5.

Reference Type BACKGROUND
PMID: 7889437 (View on PubMed)

Cook PJ, Flanagan R, James IM. Diazepam tolerance: effect of age, regular sedation, and alcohol. Br Med J (Clin Res Ed). 1984 Aug 11;289(6441):351-3. doi: 10.1136/bmj.289.6441.351.

Reference Type BACKGROUND
PMID: 6432093 (View on PubMed)

Pena LR, Mardini HE, Nickl NJ. Development of an instrument to assess and predict satisfaction and poor tolerance among patients undergoing endoscopic procedures. Dig Dis Sci. 2005 Oct;50(10):1860-71. doi: 10.1007/s10620-005-2952-7.

Reference Type BACKGROUND
PMID: 16187188 (View on PubMed)

Keeffe EB, O'Connor KW. 1989 A/S/G/E survey of endoscopic sedation and monitoring practices. Gastrointest Endosc. 1990 May-Jun;36(3 Suppl):S13-8.

Reference Type BACKGROUND
PMID: 2351253 (View on PubMed)

Hirsh I, Vaissler A, Chernin J, Segol O, Pizov R. Fentanyl or tramadol, with midazolam, for outpatient colonoscopy: analgesia, sedation, and safety. Dig Dis Sci. 2006 Nov;51(11):1946-51. doi: 10.1007/s10620-006-9413-9. Epub 2006 Sep 29.

Reference Type BACKGROUND
PMID: 17009113 (View on PubMed)

Tu RH, Grewall P, Leung JW, Suryaprasad AG, Sheykhzadeh PI, Doan C, Garcia JC, Zhang N, Prindiville T, Mann S, Trudeau W. Diphenhydramine as an adjunct to sedation for colonoscopy: a double-blind randomized, placebo-controlled study. Gastrointest Endosc. 2006 Jan;63(1):87-94. doi: 10.1016/j.gie.2005.08.015.

Reference Type BACKGROUND
PMID: 16377322 (View on PubMed)

Roach CL, Husain N, Zabinsky J, Welch E, Garg R. Moderate sedation for echocardiography of preschoolers. Pediatr Cardiol. 2010 May;31(4):469-73. doi: 10.1007/s00246-009-9622-z. Epub 2010 Jan 3.

Reference Type BACKGROUND
PMID: 20047024 (View on PubMed)

Hofmeister EH, Egger CM. Evaluation of diphenhydramine as a sedative for dogs. J Am Vet Med Assoc. 2005 Apr 1;226(7):1092-4. doi: 10.2460/javma.2005.226.1092.

Reference Type BACKGROUND
PMID: 15825733 (View on PubMed)

Husain Z, Hussain K, Nair R, Steinman R. Diphenhydramine induced QT prolongation and torsade de pointes: An uncommon effect of a common drug. Cardiol J. 2010;17(5):509-11.

Reference Type BACKGROUND
PMID: 20865683 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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DAASIPCO

Identifier Type: -

Identifier Source: org_study_id

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