Effect of the Antihistamine Injection to Prevent Paradoxical Reaction During Sedative Endoscopy

• ClinicalTrials.gov Identifier: NCT03940391
• Recruitment Status: Enrolling by invitation
• First Posted: May 7, 2019
• Last Update Posted: April 17, 2020
• Sponsor: Seoul National University Hospital
• Information provided by (Responsible Party): Su Jin Chung, Seoul National University Hospital

Study Description

Brief Summary:

This single-blind prospective study is aimed to investigate the effect of antihistamine as an adjunctive sedative for the patients with histories of severe paradoxical reaction to midazolam during sedative endoscopy. Participating patients are to receive antihistamine intravenously in addition to midazolam. The primary outcome is the reduction of paradoxical reaction in the antihistamine combination group. The secondary outcome is to compare sedation quality, performance quality, reduction of total midazolam dose will be analyzed between antihistamine combination and midazolam only group.

Condition or disease	Intervention/treatment	Phase
Endoscopy	Drug: Chlorpheniramine and midazolam; Drug: Midazolam	Not Applicable

Detailed Description:

The present study will be conducted at Seoul National University Hospital Gangnam center between May 2019 and April 2020. Participants who have histories of paradoxical reaction to sedative endoscopy in medical record gave consent on the day of the endoscopy and were assigned to receive the combination of chlorpheniramine (4-6mg) with midazolam(1-10mg) Meanwhile, the patients do not want the use of chlorpheniramine and were assigned to midazolam alone as routine clinical practice. Research medication (chlorpheniramine) was administered 2 to 3 minutes before the administration of midazolam outside of endoscopy room. The blinded endoscopist and assistant nurse are going to perform induction for moderate sedation using incremental doses of the intravenous midazolam (1-2 mg) given every 2 minutes. The endoscopists and assistant nurses will assess the occurrence of severe paradoxical reaction (Grade 3) and other major quality outcomes (procedure/intubation time, sedation quality, completeness of procedure [10 Key image documentation], the satisfaction of procedure, side effects). The endoscopists and nurses will individually rate outcome measure using a 5-point Likert scale.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 220 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Prevention
• Official Title: Effect of an Adjunctive Sedative for the Patients With Histories of Paradoxical Reaction to Midazolam During Sedative Endoscopy
• Actual Study Start Date: May 1, 2019
• Estimated Primary Completion Date: April 14, 2020
• Estimated Study Completion Date: April 14, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: antihistamine combination; Participants in this group will get combination chlorpheniramine and midazolam injection for sedative endoscopy.	Drug: Chlorpheniramine and midazolam; Administration of chlorpheniramine injection as an adjunctive sedative during sedative endoscopy.
Placebo Comparator: midazolam; Participants in this group will get only midazolam injection for sedative endoscopy	Drug: Midazolam; Administration of midazolam as a sedative during sedative endoscopy as routine clinical practice.

Outcome Measures

Primary Outcome Measures :

1. Occurrence of severe paradoxical reaction (>= level 3) [ Time Frame: 1 day ]
   (1) irrational talking or increased talkativeness such as mumbling to himself/herself; (2) restlessness or loss of cooperation such as resisting the insertion of endoscope or trying to bite the scope; (3) excessive movement requiring repositioning such as jerking or swinging movements of the arms and legs or trying to draw out the scope or mouthpiece; and (4) hostile action such as trying to strike the endoscopists or attending nurses.

Secondary Outcome Measures :

1. procedure/intubation time [ Time Frame: 1 day ]
   procedural time (time from scope insertion to scope out) Intubation time (time from scope insertion to upper esophagus)
2. Dose of midazolam [ Time Frame: 1 day ]
   total amount of benzodiazepine
3. completeness of procedure [ Time Frame: 1 day ]
   photo documentation of key anatomical area
4. Satisfaction for Quality of sedation [ Time Frame: 1 day ]

   5-point Likert scale : endoscopists and assistant nurses

   1. Strongly unsatisfied
   2. Unsatisfied
   3. Neither satisfied nor unsatisfied
   4. Satisfied
   5. Strongly satisfied
5. Satisfaction for the procedure [ Time Frame: 1 day ]

   5-point Likert scale for pain and sedation: patients

   1. Strongly unsatisfied
   2. Unsatisfied
   3. Neither satisfied nor unsatisfied
   4. Satisfied
   5. Strongly satisfied
6. adverse events [ Time Frame: 1 day ]
   hypoxia, arrythmia, low blood pressure and administration of antidote

Eligibility Criteria

• Ages Eligible for Study: 19 Years to 69 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Previous histories of the paradoxical reaction during a sedative endoscopic examination

Exclusion Criteria:

• inability to execute informed consent
• allergic to antihistamine agent
• pregnancy
• severe cardiopulmonary disease
• prior administration of antihistamine on the same day

Contacts and Locations

Locations

Korea, Republic of

Healthcare System Gangnam Center, Seoul National University Hospital

Seoul, Korea, Republic of

Sponsors and Collaborators

Seoul National University Hospital

More Information

Publications of Results:

Sachar H, Pichetshote N, Nandigam K, Vaidya K, Laine L. Continued midazolam versus diphenhydramine in difficult-to-sedate patients: a randomized double-blind trial. Gastrointest Endosc. 2018 May;87(5):1297-1303. doi: 10.1016/j.gie.2017.01.028. Epub 2017 Jan 31.

Nusrat S, Madhoun MF, Tierney WM. Use of diphenhydramine as an adjunctive sedative for colonoscopy in patients on chronic opioid therapy: a randomized controlled trial. Gastrointest Endosc. 2018 Oct;88(4):695-702. doi: 10.1016/j.gie.2018.04.2342. Epub 2018 Apr 22.

Tae CH, Kang KJ, Min BH, Ahn JH, Kim S, Lee JH, Rhee PL, Kim JJ. Paradoxical reaction to midazolam in patients undergoing endoscopy under sedation: Incidence, risk factors and the effect of flumazenil. Dig Liver Dis. 2014 Aug;46(8):710-5. doi: 10.1016/j.dld.2014.04.007. Epub 2014 Jun 2.

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.

• Responsible Party: Su Jin Chung, Professor, Seoul National University Hospital
• ClinicalTrials.gov Identifier: NCT03940391
• Other Study ID Numbers: H-1093-054-1017
• First Posted: May 7, 2019
• Last Update Posted: April 17, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Su Jin Chung, Seoul National University Hospital:

paradoxical reaction; midazolam

Additional relevant MeSH terms:

Chlorpheniramine; Midazolam; Adjuvants, Anesthesia; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; GABA Modulators; GABA Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antipruritics; Dermatologic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Anti-Allergic Agents