Efficacy and Safety of Dexmedetomidine During Weaning From Analgesia and Sedation in PICU (TIP-15-01)

Withdrawal Syndrome Clinical Trial

— TIP-15-01  

Official title:

Efficacy and Safety of Dexmedetomidine During Weaning From Analgesia and Sedation in Pediatric Intensive Care Unit. A Multicenter, Double-blind, Randomized Controlled Trial.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03645603
• Other study ID #: EudraCT 2015-002114-80 OsSC
• Status: Terminated
• Phase: Phase 2
• Start date: August 30, 2018
• Est. completion date: January 18, 2020

Study information

• Verified date: October 2021
• Source: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This interventional study evaluates the efficacy of dexmedetomidine during weaning from analgesic and sedative drugs in reducing the occurrence of the withdrawal syndrome in PICU. All enrolled patients will undergo the same weaning regimen one half will receive dexmedetomidine while the other will receive a placebo.

Description:

Children admitted to PICU need of analgesic and sedative drugs. Prolonged treatment can lead to undesirable effects as dependence and tolerance. Patients that have developed dependence may develop the withdrawal syndrome (WS) during the analgesics and sedatives weaning process.

Withdrawal symptoms are due to central nervous system excitement, gastrointestinal disturbance, and sympathetic system activation. The incidence of withdrawal syndrome is variable between 17 and 57% a recent study reported an incidence of 64.6% of WS in Italian PICUs. The prevention strategies are addressed to the restriction of drug exposure and to the gradual tapering of infusion. However, these strategies have weak evidence of effectiveness. In this study, the investigators hypothesize that dexmedetomidine may be useful and effective during the weaning of analgosedation drugs in PICU, in preventing the withdrawal syndrome. The primary aim of the study is to evaluate the efficacy of dexmedetomidine in reducing the occurrence of the WS. Secondary aims are to evaluate the dexmedetomidine safety during the weaning, the effective dose range, and the efficacy in reducing the duration of the weaning, of the mechanical ventilation, and of the length of PICU stay. Efficacy will be compared among pediatric age groups, gender, race, Pediatric Index of Mortality (PIM3) score, and length of the analgosedation treatment.

Patients admitted to the PICU that meets the inclusion criteria, will be randomly assigned to one of the two treatment groups: treatment A (dexmedetomidine) or treatment B (placebo).

Twenty-four hours before the start of the weaning an intravenous infusion of dexmedetomidine/placebo will start. After 24 hours of dexmedetomidine infusion, the weaning regimen will begin following the subsequent indications: 10% reduction of the dose every 12 hours. The withdrawal assessment tool version 1 (WAT-1) is the selected scale to evaluate the occurrence of the WS. Patients with a score of WAT-1 <3 continue the weaning regimen. Patients with a score ≥3 increase the dose of dexmedetomidine/placebo until the next WAT-1 score control and temporarily stop the planned 10% dose reduction. If the next WAT-1 score decreased by at least 1 point from the previous score, the weaning program restarted (10% reduction) without further changes in the dose of dexmedetomidine/placebo until the subsequent score. The 'acute withdrawal crisis' will be treated with a rescue dose of the opioid and/or benzodiazepine in use repeatable until resolution of the crisis. Once analgesics and sedatives weaning is complete, dexmedetomidine will gradually discontinue. Five days after discharge from PICU, a follow-up visit will be performed.

The sample size estimate is 80 participants for each of the two groups for a total of 160 patients recruited within a period of two years.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 45
• Est. completion date: January 18, 2020
• Est. primary completion date: January 18, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

Inclusion Criteria:

• Continuous analgesic and sedative endovenous treatment for at least 5 days

• Invasive or non-invasive mechanical ventilation

• Clinical conditions that allow by clinical judgment the start of analgosedation weaning

• Post-natal age = 7 days and PMA beyond the 37 weeks

• Written informed consent obtained

Exclusion Criteria:

• Hemodynamic instability

• Cardiac bundle-branch block of 2 or 3 degree

• Hypersensitivity to the alpha-agonists

• Persistent fever of unknown origin or sensitivity to malignant hyperthermia

• Use of alpha-agonist (clonidine or dexmedetomidine) in the last 30 days

Related Conditions & MeSH terms

• Substance Withdrawal Syndrome
• Withdrawal Syndrome

Intervention

Drug:
• Dexmedetomidine
intravenous infusion
• Placebo
intravenous infusion of physiological saline solution to mimic dexmedetomidine infusion

Locations

Country	Name	City	State
Italy	PICU Policlinico S.Orsola-Malpighi	Bologna

Sponsors (3)

Lead Sponsor	Collaborator
IRCCS Azienda Ospedaliero-Universitaria di Bologna	Azienda Ospedaliera di Padova, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Country where clinical trial is conducted

Italy, 

References & Publications (1)

Amigoni A, Mondardini MC, Vittadello I, Zaglia F, Rossetti E, Vitale F, Ferrario S, Savron F, Coffaro G, Brugnaro L, Amato R, Wolfler A, Franck LS; Network of Paediatric Intensive Care Unit Study Group (TIPNet). Withdrawal Assessment Tool-1 Monitoring in — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Opioid dose	verification of adherence to weaning regimen	7 days
Other	Change in Sedative dose	verification of adherence to weaning regimen	7 days
Primary	Change in Withdrawal Assessment Tool (WAT-1) scale	WAT-1 score recorded every 12 hours.The score ranges from 0 to 12, a score =3 indicates the presence of signs/symptoms of withdrawal.	time 0 start dexmedetomidine and every 12 hours post-start dexmedetomidine for 7 days
Secondary	Change in heart rate	changes in heart rate will be recorded when their value differs more than 20% by the patient's baseline values.	0,1, 2, 12, 24 hours post-start dexmedetomidine and then every 12 hours for 7 days
Secondary	Change in Systolic Blood Pressure	changes in Systolic Blood Pressure will be recorded when their value differs more than 20% by the patient's baseline values.	0,1, 2, 12, 24 hours post-start dexmedetomidine and then every 12 hours for 7 days
Secondary	Change in Diastolic Blood Pressure	changes in Diastolic Blood Pressure will be recorded when their value differs more than 20% by the patient's baseline values.	0,1, 2, 12, 24 hours post-start dexmedetomidine and then every 12 hours for 7 days