Dexmedetomidine vs Placebo for Pediatric Cleft Palate Repair

February 4, 2019 updated by: Chris Glover, Baylor College of Medicine

A Randomized, Double-Blinded, Placebo Controlled Trial Using Single Dose Dexmedetomidine In The Treatment Of Pain In Patients Undergoing Cleft Palate Repair

The primary objective of this study is to evaluate the efficacy of administering intravenous dexmedetomidine as a single preemptive dose to placebo in reducing the total 24 hour dose of opioids as measured on a weight adjusted morphine equivalent basis.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

The eligibility of the patient to participate in this study will be determined by the Investigator on the basis of the inclusion and exclusion criteria. Consent will be obtained from eligible patients only.

The following is the standard intraoperative anesthesia protocol utilized at Texas Children's Hospital for all children undergoing this procedure of cleft palate repair even if they are not part of the study: (1) Induction of anesthesia via a face mask with sevoflurane 6-8% and 70% N2O / 30% O2 (2) A peripheral IV will be inserted and glycopyrrolate 5-10 mcg/kg IV administered to dry oral secretions and reduce vagal responses. (3) Tracheal intubation using appropriate equipment in keeping with the clinical judgment of the anesthesia care provider. The protocol will permit the administration of propofol up to 3 mg/kg over 20-30 seconds to increase the depth of anesthesia prior to tracheal intubation if the Attending Anesthesiologist deems it necessary. (4) General anesthesia maintained with Sevoflurane/isoflurane with inhaled concentrations adjusted to keep blood pressure and heart rates within 20% of baseline. (5) Nitrous oxide will be discontinued and the lowest inspired oxygen concentration will be administered to reduce risks of airway fires while avoiding hypoxemia. (6) Fentanyl 1-2 mcg/kg administered at the start of the procedure with subsequent fentanyl 1 mcg/kg boluses as needed if the heart rate and blood pressure are increased per vital signs (HR and BP) variance greater than 20% of baseline (7) Dexamethasone 0.5 mg/kg IV. (8) Rocuronium 0.6 -1 mg/kg IV may be administered for paralysis if this is clinically indicated in the opinion of the Attending Anesthesiologist. (9) Local infiltration with 0.5% lidocaine with 1:200,000 epinephrine will be administered by the surgeon at the site of the palatoplasty in keeping with our current surgeon practice. (10) Ondansetron 0.1 mg/kg IV at the end of the procedure (11) Anesthetic gases will be discontinued at the end of the procedure and 100% oxygen administered prior to tracheal extubation. If rocuronium was used neuromuscular blockade will be antagonized with neostigmine 0.07 mg/kg and glycopyrrolate 10 mcg/kg. The timing of tracheal extubation will be based on clinical indications and the judgment of the Attending Anesthesiologist.

The above standardized management will be followed for all children undergoing this operation even if they are not part of the study. The experimental part of the protocol will involve randomization of subjects in a 1:1 ratio to receive intravenous dexmedetomidine or placebo. Randomization will occur by the pharmacy using a computer generated random number. The study will be double-blind with respect to the treatment assignment. The investigational pharmacy will mix and deliver either dexmedetomidine 1 mcg/kg in a concentration of 4 mcg/ml or placebo to the anesthesia provider on the day of surgery. The assigned study drug will be administered when the heart rate and blood pressure have returned to acceptable stable levels after tracheal intubation and before the surgeon has started the palatal injection of lidocaine with epinephrine. Placebo or dexmedetomidine will be administered in a similar fashion as an IV infusion over 10 minutes as recommended to avoid bradycardia,hypertension, hypotension or other cardiac events. . Persistent bradycardia (greater than 30% reduction from baseline for more than 1 minute) will be managed with administration of atropine 0.01 mg/kg. An immediate rise in blood pressure will be treated with an increase in the inspired concentration of inhaled anesthetics. If there is hypertension (greater than 30% rise in value from baseline), the inspired concentration of inhaled anesthetics will be increased. Persistent hypotension (greater than 30% decrease from baseline levels for more than 1 minute) will be treated with fluid bolus of 5-10 ml/kg and decreasing the concentration of the volatile anesthetic. Other drugs may be used in keeping with the clinical judgment of the Attending Anesthesiologist.

Postoperative management will not be changed for the purposes of the study. In keeping with standard practices in the TCH, all patients in the PACU will be monitored with continuous pulse oximetry, EKG and serial non-invasive blood pressure measurements. Pain will be assessed using an age appropriate observational scale- the FLACC score for younger patients and the FACES score for older co-operative patients. Pain scores are recorded on arrival to the PACU, when awake and at 30 minute intervals. If the FLACC score is greater than 4 or the FACES greater than 2, patients will receive morphine 25 mcg/kg IV to be repeated as required in 10 minutes if adequate pain control has not been achieved. Supplemental oxygen will be administered till the child can maintain an oxygen saturation greater than 92% in room air. Emergence delirium will be determined using the PAED score and children with scores of greater than 12 will receive therapy in keeping with the clinical judgment of the Attending Anesthesiologist (additional opioids or IV propofol). The child will be discharged to the floor when awake, can maintain patency of the airway, have stable vital signs, a pain score less than 4 and an Aldrete score of at least 9.

Patients will be transferred to the floor where they will receive the current standard postoperative regimen used by our plastic surgery service care for this procedure. This will includeHycet 0.135mg/kg every 4 hours when needed. Morphine 0.025 mg/kg IV every 4 hours will be made available as a rescue analgesia for break through pain. Nurses record pain scores on the FLACC or FACES scale depending on the age of the patient and ability to cooperate. Rescue analgesia will be provided based on a nursing assessment that the pain is poorly controlled (FLACC score greater than 4 or FACES score greater than 2) after receiving oral pain medications. Non -steroidal anti-inflammatory drugs are usually avoided in these children because of concerns for bleeding from the raw mucosal surfaces at the site of the surgery.

We will record all perioperative, intraoperative and postoperative drugs administered to patients, pain scores, Pediatric Anesthesia Emergence Delirium (PAED) scores in the PACU, pain scores and rescue medications administered during the stay in the PACU and on the floor. The time to first rescue medication, oral intake, and discharge from the PACU and the hospital will also be recorded along with adverse events such as vomiting, constipation, pruritis, agitation, respiratory depression or excessive sedation. Any interventions to treat these will be noted.

Study Type

Interventional

Phase

  • Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 12 years (Child)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients between 6mo to 8 years of age scheduled to undergo primary or secondary cleft repair.

Exclusion Criteria:

  • Patients with significant cognitive impairment
  • Patients with various syndromes known to be associated with difficult airways(e.g. Goldenhar's syndrome, Treacher- Collins, Trisomy 13 or 18, Pierre Robin, etc.)
  • Have a prior history of allergy, hypersensitivity or contraindication to any drug used for anesthesia including opioids (morphine, fentanyl, hydrocodone) and inhalation agents(i.e. children with susceptibility to malignant hyperthermia)
  • Have a history of congenital bleeding diathesis(e.g. hemophilia) or any active clinically significant bleeding, impaired renal or hepatic function
  • Children with heart failure, heart block, ventricular dysfunction, cardiomyopathy, myocarditis or congenital heart disease where cardiac output is rate dependent and relies on A-V synchrony (e.g. single ventricle). Children with well controlled atrial or ventricular septal defects, patent ductus arteriosus, repaired coarctation of the aorta will qualify if they have no cardiac rhythm or hypertension problems.
  • Children with uncontrolled hypertension, intracranial vascular malformations, Moya Moya disease or intracranial hypertension.
  • Any child who has received an investigational drugs within 30 days before study drug administration.
  • Inability of the parent or legal guardian to understand the requirements of the study or be unwilling to provide written informed consent (as evidenced by signature on an informed consent document approved by an Institutional Review Board) and agree to abide by the study restrictions.
  • Be otherwise unsuitable for the study, in the opinion of the Investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental group
Intervention group 1: pre-operative administration of IV dexmedetomidine 1mcg/kg
Drug: Dexmedetomidine
Analgesic Efficacy
Other Names:
  • Precedex
Placebo Comparator: Placebo group
Intervention group 2: placebo
Drug: Placebo
Saline placebo
Other Names:
  • Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Postoperative pain control
Time Frame: 24 hours
Assessment of and clinical measurement that one treatment group will be better with postoperative pain management than the non-treatment group, which would be similar to published data for children undergoing this procedure. This will be measured in a mean pain score. There will be integrating of pain scores and morphine consumption.
24 hours
Opioid consumption
Time Frame: 24 hours
Opioid consumption is measured in mean morphine equivalent dose in mcg/kg, this will be integrated with the pain scores.
24 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The number of children with FLACC scores greater than 4
Time Frame: 24 hours
FLACC Pain Scores
24 hours
Time to first rescue analgesia
Time Frame: 24 hours
Time in minutes to administration of first dose of rescue analgesia
24 hours
Respiratory depression
Time Frame: 24 hours
Patients with SPO2 less than 85%
24 hours
Postoperative vomiting
Time Frame: 24 hours
postoperative emesis
24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Baylor College of Medicine

Investigators

  • Principal Investigator: Chris D. Glover, MD, Baylor College of Medicine - Texas Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

December 31, 2017

Primary Completion (Anticipated)

December 1, 2019

Study Completion (Anticipated)

December 1, 2019

Study Registration Dates

First Submitted

September 23, 2016

First Submitted That Met QC Criteria

September 23, 2016

First Posted (Estimate)

September 26, 2016

Study Record Updates

Last Update Posted (Actual)

February 5, 2019

Last Update Submitted That Met QC Criteria

February 4, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-34431

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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