Clinical Study to Investigate the Efficacy and the Safety of DA-9501 in Sedation During the Surgery With Epidural Anesthesia or Spinal Anesthesia Without Intubation

Phase III Randomized Placebo-controlled Double Blind Comparative Study to Investigate the Efficacy and Safety of DA-9501 in Sedation During the Surgery With Epidural Anesthesia or Spinal Anesthesia Without Intubation Under Monitored Sedation Care

The purpose of this study is to examine the efficacy and safety of DA-9501 (Dexmedetomidine) in patients who require sedation during the surgery that requires epidural or spinal anesthesia without intubation under monitored sedation care.

Study Overview

• Status: Completed
• Conditions: Sedation
• Intervention / Treatment: Drug: Placebo; Drug: Dexmedetomidine hydrochloride

Detailed Description

Phase III, randomized, placebo controlled, double blind, parallel comparative study (Therapeutic confirmatory trial), to evaluate the efficacy and the safety of Dexmedetomidine in non-intubated patients who require sedation during surgery with spinal or epidural anesthesia under monitored sedation care

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Kyoto, Japan
    • Japanese Red Cross Kyoto Daini Hospital
  • Miyazaki, Japan
    • University of Miyazaki Hospital
  • Okayama, Japan
    • Okayama University Hospital
  • Osaka, Japan
    • Kitano Hospital, The Tazuke Kofukai Medical Research Institute
  • Tokyo, Japan
    • Nippon Medical University Hospital
  • Aichi
    • Nagoya, Aichi, Japan
      • Nagoya University Hospital
  • Hokkaido
    • Asahikawa, Hokkaido, Japan
      • Asahikawa Medical University Hospital
    • Sapporo, Hokkaido, Japan
      • Sapporo Medical University Hospital
  • Kochi
    • Nangoku, Kochi, Japan
      • Kochi Medical School Hospital
  • Nagano
    • Matsumoto, Nagano, Japan
      • Shinshul University Hospital
  • Shimane
    • Izumo, Shimane, Japan
      • Shimane University Hospital
  • Tottori
    • Yonago, Tottori, Japan
      • Tottori University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient has signed and dated the Informed Consent after the study had been fully explained.
2. Patient is male or female, at least 20 years of age when the Informed Consent is obtained.
3. American Society for Anesthesiologists (ASA) I to III Class.
4. Patient who requires sedation during the elective surgery which requires ≥30mins (expected time) without intubation under monitored sedation care.
5. Patient undergoing a surgery requiring epidural or spinal anesthesia

Exclusion Criteria:

1. Patient who underwent general anesthesia within 7 days, or who received other study drugs within 30 days from the date of consent.
2. Patient with <92% SpO2, at the physical examination prior to the study drug administration, or ventilatory failure which requires intubation or Laryngeal Mask.
3. Patient with central nervous system pathology which may lead to increased intracranial pressure, uncontrolled seizures, psychiatric disorder which may be confused with the response to sedation treatment.
4. Patient who require general anesthesia.
5. Patient who receives treatment by alpha-2 agonists or alpha-2 antagonists within seven days of scheduled surgery or procedure.
6. Patient in whom opioids, DA-9501 or other alpha-2 agonists, or drugs which may be used in the study are contraindicated.
7. Patient diagnosed with unstable angina or acute myocardiac infarction within 6 weeks from the date of consent.
8. Patient whose heart rate is <60 bpm, systolic blood pressure is <90 mmHg by the physical examination prior to the study drug administration.
9. Patient has third degree heart block, unless the patient has a pacemaker or transverse pacing wires are in place.
10. Patient who has experienced an increase in alanine transaminase (ALT) and / or aspartate aminotransferase (AST) more than double the upper normal limit within 2 months of the date of consent, or who has a history of liver insufficiency.
11. Pregnant or lactating woman.
12. In the Investigator's or subinvestigator's opinion, the patient has any symptom or condition which might increase risk to the patient by conducting the study or preclude obtaining satisfactory study data

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Dexmedetomidine 0 mcg/kg/hr 10 min Initial dose + Dexmedetomidine 0 mcg/kg/hr Maintenance dose	Drug: Placebo
Experimental: Dexmedetomidine 0.067 mcg/kg; Dexmedetomidine 0.4 mcg/kg/hr 10 min Initial dose + Dexmedetomidine 0.2 - 0.7 mcg/kg/hr Maintenance dose	Drug: Dexmedetomidine hydrochloride; Dexmedetomidine 0.2 to 0.7 mcg/kg/hr
Experimental: Dexmedetomidine 0.25 mcg/kg; Dexmedetomidine 1.5 mcg/kg/hr 10 min Initial dose + Dexmedetomidine 0.2 - 0.7 mcg/kg/hr Maintenance dose	Drug: Dexmedetomidine hydrochloride; Dexmedetomidine 0.2 to 0.7 mcg/kg/hr
Experimental: Dexmedetomidine 0.5 mcg/kg; Dexmedetomidine 3 mcg/kg/hr 10 min Initial dose + Dexmedetomidine 0.2 - 0.7 mcg/kg/hr Maintenance dose	Drug: Dexmedetomidine hydrochloride; Dexmedetomidine 0.2 to 0.7 mcg/kg/hr
Experimental: Dexmedetomidine 1.0 mcg/kg; Dexmedetomidine 6 mcg/kg/hr 10 min Initial dose + Dexmedetomidine 0.2 - 0.7 mcg/kg/hr Maintenance dose	Drug: Dexmedetomidine hydrochloride; Dexmedetomidine 0.2 to 0.7 mcg/kg/hr

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Patients Who Did Not Require Rescue Administration of Propofol to Achieve and Maintain Observer's Assessment of Alertness/Sedation (OAA/S) Score ≤4 During the Study Drug Administration.	Pre-dose, every 5 ± 2 minutes after start of study drug infusion and every 15 ± 2 minutes until 1 hour after study drug infusion. Before additional administration of sedative.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Propofol Dosing Required to Achieve and Maintain OAA/S Score ≤4 During the Study Drug Administration		15 minutes after the start of study drug, if the OAA/S score is 5.
Dosage of Propofol Dosing Required to Achieve and Maintain OAA/S Score ≤4 During the Study Drug Administration		15 minutes after the start of study drug, if the OAA/S score is 5.
Time to First Rescue Administration of Propofol		During the study drug infusion period (≥15 minutes [Approximate])
Percentage of Patients Who Did Not Require Rescue Administration of Fentanyl During the Study Drug Administration		After the surgery start, the administration of fentanyl is permissible as required to treat pain. In case of repeated dose, the dosing interval should be ≥15 minutes.
Number of Fentanyl Dosing Required During the Study Drug Administration.		During the study drug administration
Dosage of Fentanyl Dosing Required During the Study Drug Administration.		During the study drug administration
Percentage of Time Spent OAA/S Score ≤4 During the Study Drug Infusion		Pre-dose, every 5 ± 2 minutes after start of study drug infusion and every 15 ± 2 minutes until 1 hour after study drug infusion. Before additional administration of sedative.
Percentage of Time Spent OAA/S Score 3 to 4 During the Study Drug Infusion		Pre-dose, every 5 ± 2 minutes after start of study drug infusion and every 15 ± 2 minutes until 1 hour after study drug infusion. Before additional administration of sedative.
Time to Attain the Point Where Patient is Recovered Assessed by Aldrete Score Following Discontinuation of the Study Drug Infusion		Every 15 ± 2 minutes until the score of each item becomes ≥1 and the total value becomes ≥8.
Visual Analogue Scale (VAS) Score Evaluation by Investigator or Sub-investigator (Easiness of Maintenance of Sedation Level)	VAS score ranges from 0 to 10, with 0 being the better/preferred outcome. Low values indicated more ease of maintenance of sedation level.	Within 24 hours after completion of the study drug administration
Visual Analogue Scale (VAS) Score Evaluation by Investigator or Sub-investigator (Stability of Hemodynamic State)	VAS score ranges from 0 to 10, with 0 being the better/preferred outcome. Low values indicated more ease of maintenance of sedation level.	Within 24 hours after completion of the study drug administration
Visual Analogue Scale (VAS) Score Evaluation by Investigator or Sub-investigator (Stability of Respiratory State)	VAS score ranges from 0 to 10, with 0 being the better/preferred outcome. Low values indicated more ease of maintenance of sedation level.	Within 24 hours after completion of the study drug administration
Visual Analogue Scale (VAS) Score Evaluation by Investigator or Sub-investigator (Subject's Cooperation)	VAS score ranges from 0 to 10, with 0 being the better/preferred outcome. Low values indicated more ease of maintenance of sedation level.	Within 24 hours after completion of the study drug administration
Score Evaluation of Satisfaction and Anxiety of the Subject ("I Was Satisfied With This Anesthesia Procedure")	Rating: 1 is the better/preferred value for scores from 1 to 4. Low values indicated more ease of maintenance of sedation level.	Within 24 hours after completion of the study drug administration (as much as possible)
Score Evaluation of Satisfaction and Anxiety of the Subject ("I Did Not Feel Pain During the Surgery")	Rating: 1 is the better/preferred value for scores from 1 to 4. Low values indicated more ease of maintenance of sedation level.	Within 24 hours after completion of the study drug administration (as much as possible)
Score Evaluation of Satisfaction and Anxiety of the Subject ("If You May Undergo a Similar Surgery, the Same Anesthesia Procedure Will be Requested for the Next Time")	Rating: 1 is the better/preferred value for scores from 1 to 4. Low values indicated more ease of maintenance of sedation level.	Within 24 hours after completion of the study drug administration (as much as possible)
Score Evaluation of Satisfaction and Anxiety of the Subject ("Assess the Anxiety Level Before Surgery")	Rating: 1 is the better/preferred value for scores from 1 to 5. Low values indicated more ease of maintenance of sedation level.	Within 24 hours after completion of the study drug administration (as much as possible)
Score Evaluation of Satisfaction and Anxiety of the Subject ("Assess the Anxiety Level During Surgery")	Rating: 1 is the better/preferred value for scores from 1 to 5. Low values indicated more ease of maintenance of sedation level.	Within 24 hours after completion of the study drug administration (as much as possible)
Score Evaluation of Satisfaction and Anxiety of the Subject ("Assess the Anxiety Level After Surgery")	Rating: 1 is the better/preferred value for scores from 1 to 5. Low values indicated more ease of maintenance of sedation level.	Within 24 hours after completion of the study drug administration (as much as possible)

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: Maruishi Pharmaceutical

Publications and helpful links

General Publications

• Inagaki Y, Yamakage M, Sakamoto A, Okayama A, Oya N, Hiraoka T, Morita K. The Efficacy and Safety of Dexmedetomidine for Sedation During Surgery Under Epidural or Spinal Anesthesia: A Randomized, Double-Blind, Placebo-Controlled Study. Yonago Acta Med. 2022 Jan 4;65(1):14-25. doi: 10.33160/yam.2022.02.002. eCollection 2022 Feb.

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2011
• Primary Completion (Actual): November 18, 2011
• Study Completion (Actual): November 18, 2011

Study Registration Dates

• First Submitted: September 21, 2011
• First Submitted That Met QC Criteria: September 21, 2011
• First Posted (Estimate): September 22, 2011

Study Record Updates

• Last Update Posted (Actual): March 22, 2021
• Last Update Submitted That Met QC Criteria: March 19, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Sedation; spinal anesthesia; Dexmedetomidine; epidural anesthesia; Non-intubation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: DEX-303

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• product manufactured in and exported from the U.S.: Yes