Comparative Dose-Response of Intrathecal Dexmedetomidine for Post-Spinal Shivering

NCT07327879 | Not Yet Recruiting Phase 3

• 1 other identifier: RC. 2.12.2025
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Dexmedetomidine, a highly selective α2-adrenergic agonist, when used intrathecally as an adjuvant to local anesthetics, prolongs sensory/motor block and may blunt thermoregulatory shivering mechanisms. Several randomized controlled trials and meta-analyses have demonstrated decreased shivering incidence with intrathecal dexmedetomidine, but reported doses vary (commonly 2.5, 5, and 10 µg, and in some trials up to 15-20 µg), and the balance between efficacy and adverse effects (sedation, bradycardia, and hypotension) is not fully established. Hence, a head-to-head randomized comparison of several low-to-moderate intrathecal doses is warranted. Objective: to compare the safety and efficacy of three intrathecal dexmedetomidine doses (2.5 µg, 5 µg, 10 µg) versus placebo for the prevention of post-spinal shivering.

Conditions

Post-Spinal Shivering

Keywords

Intrathecal Dexmedetomidine

Outcome Measures

Primary Outcomes (1)

• Incidence of clinically significant shivering

  Incidence of clinically significant shivering within 60 minutes after spinal injection, defined as Crossley and Mahajan shivering scale grade ≥2 (scale 0-4)The highest intensity of shivering experienced by the patient, scored on the 0-4 scale. The Crossley and Mahajan shivering scale is a clinically validated, four-grade ordinal scale (0-4) used to objectively quantify the severity of post-anesthetic shivering. It is defined as follows: Grade 0 signifies no shivering; Grade 1 indicates mild, intermittent fasciculations of the face, neck, or chest; Grade 2 represents visible, intermittent shivering involving more than one muscle group; Grade 3 denotes generalized, continuous shivering of the whole body; and Grade 4 describes gross, bed-shaking tremors that interfere with monitoring or procedure. Grade ≥2 is typically considered clinically significant and often triggers therapeutic intervention. The scale is assessed through direct visual observation of the patient by trained personnel.

  Throughout the intraoperative period until 60 minutes post-spinal.

Secondary Outcomes (6)

• Time to first shivering episode

  Intraoperative period, up to 60 minutes post-spinal.

• Requirement of rescue anti-shivering drug

  Intraoperative period, as needed.

• Dose of rescue anti-shivering drug

  Intraoperative period, as needed.

• Sedation level

  Postoperative 24 hour

• Patient satisfaction

  Postoperatively (e.g., prior to discharge from PACU).

Study Arms (4)

Group P

PLACEBO COMPARATOR

Patients in this group will receive the standard spinal anesthetic consisting of hyperbaric bupivacaine 0.5% (15 mg) combined with an equivalent volume of normal saline (0.9% NaCl), containing no active dexmedetomidine. The total intrathecal injection volume will be standardized to 3.5 mL across all groups by adjusting the volume of saline added.

Drug: Group P (Placebo Control Group)

Group D2.5

EXPERIMENTAL

Patients in this group will receive the standard spinal anesthetic (15 mg hyperbaric bupivacaine 0.5%) supplemented with a low dose of 2.5 µg of dexmedetomidine. Normal saline will be added to achieve the standardized total intrathecal volume of 3.5 mL.

Drug: Group D2.5 (Low-Dose Dexmedetomidine Group)

Group D5

EXPERIMENTAL

Patients in this group will receive the standard spinal anesthetic combined with a moderate dose of 5 µg of dexmedetomidine. The total volume will be adjusted to 3.5 mL with normal saline.

Drug: Group D5 (Moderate-Dose Dexmedetomidine Group)

Group D10

EXPERIMENTAL

Patients in this group will receive the standard spinal anesthetic supplemented with a higher dose of 10 µg of dexmedetomidine, with normal saline used to standardize the total volume to 3.5 mL.

Drug: Group D10 (Higher-Dose Dexmedetomidine Group)

Interventions

Group D2.5 (Low-Dose Dexmedetomidine Group) DRUG

Patients in this group will receive the standard spinal anesthetic (15 mg hyperbaric bupivacaine 0.5%) supplemented with a low dose of 2.5 µg of dexmedetomidine. Normal saline will be added to achieve the standardized total intrathecal volume of 3.5 mL.

Group D2.5

Group D5 (Moderate-Dose Dexmedetomidine Group) DRUG

Patients in this group will receive the standard spinal anesthetic combined with a moderate dose of 5 µg of dexmedetomidine. The total volume will be adjusted to 3.5 mL with normal saline.

Group D5

Group D10 (Higher-Dose Dexmedetomidine Group) DRUG

Patients in this group will receive the standard spinal anesthetic supplemented with a higher dose of 10 µg of dexmedetomidine, with normal saline used to standardize the total volume to 3.5 mL.

Group D10

Group P (Placebo Control Group) DRUG

Patients in this group will receive the standard spinal anesthetic consisting of hyperbaric bupivacaine 0.5% (15 mg) combined with an equivalent volume of normal saline (0.9% NaCl), containing no active dexmedetomidine. The total intrathecal injection volume will be standardized to 3.5 mL across all groups by adjusting the volume of saline added. This group serves as the control to establish the baseline incidence and characteristics of post-spinal shivering and block dynamics without the intervention of the α2-adrenergic agonist.

Group P

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (age 18-75 years)
• Scheduled for ureteric stone removal surgery
• ASA(American Society of Anesthesiologists) physical status I, II, or III
• Able to provide informed consent

You may not qualify if:

• Known allergy to dexmedetomidine, bupivacaine, or other study medications
• Preexisting bradycardia (heart rate \<50 beats per minute)
• Second- or third-degree atrioventricular (AV) block without a pacemaker
• Severe hepatic dysfunction
• Uncontrolled hypotension
• Pregnancy
• Chronic use of α₂-agonists or antagonists (e.g., clonidine, tizanidine)
• Infection at the planned spinal puncture site
• Coagulopathy or bleeding disorder
• Inability to rate or communicate shivering (e.g., language barrier, cognitive impairment)

Sponsors & Collaborators

• Al-Azhar University: lead
• Benha University: collaborator

Study Sites (1)

Al-Azhar University

Cairo, Egypt, 11865, Egypt

Location

Central Study Contacts

Neveen A Kohaf, Ph.D

CONTACT

+201060383012; nevenabdo@azhar.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer of Clinical Pharmacy

Study Record Dates

• First Submitted: December 26, 2025
• First Posted: January 8, 2026
• Study Start: January 28, 2026
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: January 8, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

EG (1)