Clonidine for Tourniquet-related Pain in Children

NCT04564430 | Unknown Phase 4

• 1 other identifier: NC12547
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed as a randomized, placebo-controlled, double-blinded, clinical trial with two parallel groups. This study investigates the association between a single dose of the drug, Clonidine, and the total amount of opioid administered under and 24 hours after surgery in children undergoing orthopedic limb surgery with the use of tourniquet. The investigators hypothesize that administration of clonidine to children undergoing limb surgery with the use of inflatable tourniquets would reduce post-procedural pain. This study is a pilot to obtain an effect size. Based on this the investigators will calculate a sample size for the main trial enabling us to reach a power of 0.8 with a significans level of 0.05.

Conditions

Polydactyly Toe; Thumb Hypoplasia; Trigger Finger; Polydactyly; Fingers; Osteomyelitis of Hindfoot; Osteomyelitis of Midfoot; Congenital Talipes Equinovarus; Congenital Talipes Calcaneus; Tarsal Coalition; Club Foot; Clubfoot; Congenital Knee Deformity; Leg Length Inequality in Children; Flatfoot; Hollow Foot; Congenital Valgus Foot Deformity; Polydactylia; Polysyndactyly; Syndactyly; Thumb Aplasia; Congenital Hand and Foot Deformity; Subungual Exostosis; Finger Deformity; Toe Deformity; Osteomyelitis of the Foot; Calcaneus Deformity of Foot; Congenital Hand Deformity; Hand Deformities, Congenital; Valgus Foot Deformity; Toe Joint Deformity; Capsulitis of MTP Joint

Keywords

tourniquet; pediatric; clonidine; orthopedic surgery

Outcome Measures

Primary Outcomes (1)

• Total morphine T24

  Total amount of i.v. morphine in milligram (mg) administered per kg bodyweight from end-of-incision-time (T0) through the first 24 hours postoperatively (T24).

  Through time spent in the Post-Anaesthesia Care Unit (PACU), i.e. from end-of-incision time to time of transferal from PACU to the paediatric ward, maxium up to 24 hours

Secondary Outcomes (5)

• Morphine recovery to transferal to pediatric ward

  Through time spent at the paediatric ward, i.e. from time of transferal from PACU to the paediatric ward to time of discharge up to 24 hours after end-of-incision-time

• Morphine at pediatric ward to T24

  Through time spent in the Post-Anaesthesia Care Unit (PACU), i.e. from end-of-incision time to time of transferal from PACU to the paediatric ward, maximum up to 24 hours

• Total time at recovery

  Through time spent in the Post-Anaesthesia Care Unit (PACU), i.e. from end-of-incision time to time of transferal from PACU to the paediatric ward, maximum up to 24 hours

• Maximal pain

  Through time spent in the Post-Anaesthesia Care Unit (PACU), i.e. from end-of-incision time to time of transferal from PACU to the paediatric ward, maximum up to 24 hours

• Occurrence of emergence delirium(ED)

  Through time spent in the Post-Anaesthesia Care Unit (PACU), i.e. from end-of-incision time to time of transferal from PACU to the paediatric ward, maximum up to 24 hours

Study Arms (2)

Control group

PLACEBO COMPARATOR

IV Saline (Natriumklorid B.Braun 9mg/ml, B.Braun Melsungen AG, Melsungen, Tyskland) in an equal quantity as the study drug is administered at tourniquet inflation

Other: Saline

Intervention group

EXPERIMENTAL

Catapressan (CatapresR Ampoules 150 micrograms in 1ml, Solution for injection, Boehringer Ingelheim Ltd., Berkshire, UK)(3mcg/kg) is administered at tourniquet inflation

Drug: Catapresan

Interventions

Catapresan DRUG

The intervention is either a single intravenous bolus of 3mcg/kg Catapresan (150mcg/1ml) or an equal amount of saline at the time of tourniquet inflation.

Also known as: Clonidine

Intervention group

Saline OTHER

controlgroup receiving saline

Control group

Eligibility Criteria

• Age: 3 Months - 15 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• ASA I + II
• Scheduled for GA and planned for relevant surgical procedure (according to table 1)
• Planned use of surgical tourniquet on upper and/or lower extremity

You may not qualify if:

• parental consent missing
• ASA classification \>II
• Known diagnosis of QT-prolongation syndrome
• known allergies to clonidine
• known allergies or intolerance to morphine
• daily use of pain killers
• under treatment with antihypertensive and antiarrythmic medications
• status of current or previous prematurity
• planned for peripheral or central nerve block in addition to general anaesthesia

Sponsors & Collaborators

• Odense University Hospital: lead
• Odense Patient Data Explorative Network: collaborator

Study Sites (1)

Odense University Hospital

Odense, Fyn, 5000, Denmark

RECRUITING

Related Publications (23)

• Budic I, Pavlovic D, Kitic D, Kocic G, Cvetkovic T, Simic D, Jevtovic-Stoimenov T. Tourniquet-induced ischemia-reperfusion injuries during extremity surgery at children's age: impact of anesthetic chemical structure. Redox Rep. 2013;18(1):20-6. doi: 10.1179/1351000212Y.0000000037.

  PMID: 23394494 BACKGROUND

• Kumar K, Railton C, Tawfic Q. Tourniquet application during anesthesia: "What we need to know?". J Anaesthesiol Clin Pharmacol. 2016 Oct-Dec;32(4):424-430. doi: 10.4103/0970-9185.168174.

  PMID: 28096570 BACKGROUND

• Kruse H, Christensen KP, Moller AM, Gogenur I. Tourniquet use during ankle surgery leads to increased postoperative opioid use. J Clin Anesth. 2015 Aug;27(5):380-4. doi: 10.1016/j.jclinane.2015.03.034. Epub 2015 May 12.

  PMID: 25979462 BACKGROUND

• Rudkin AK, Rudkin GE, Dracopoulos GC. Acceptability of ankle tourniquet use in midfoot and forefoot surgery: audit of 1000 cases. Foot Ankle Int. 2004 Nov;25(11):788-94. doi: 10.1177/107110070402501106.

  PMID: 15574237 BACKGROUND

• Budic I, Pavlovic D, Kocic G, Cvetkovic T, Simic D, Basic J, Zivanovic D. Biomarkers of oxidative stress and endothelial dysfunction after tourniquet release in children. Physiol Res. 2011;60(Suppl 1):S137-45. doi: 10.33549/physiolres.932170. Epub 2011 Jul 19.

  PMID: 21777032 BACKGROUND

• Estebe JP, Davies JM, Richebe P. The pneumatic tourniquet: mechanical, ischaemia-reperfusion and systemic effects. Eur J Anaesthesiol. 2011 Jun;28(6):404-11. doi: 10.1097/EJA.0b013e328346d5a9.

  PMID: 21502865 BACKGROUND

• Gourdin M, Dubois P, Mullier F, Chatelain B, Dogne JM, Marchandise B, Jamart J, De Kock M. The effect of clonidine, an alpha-2 adrenergic receptor agonist, on inflammatory response and postischemic endothelium function during early reperfusion in healthy volunteers. J Cardiovasc Pharmacol. 2012 Dec;60(6):553-60. doi: 10.1097/FJC.0b013e31827303fa.

  PMID: 22987052 BACKGROUND

• Jellinge ME, Petersen RH. [Clonidine can reduce opioid medication during post-operative pain]. Ugeskr Laeger. 2015 Nov 30;177(49):V05150415. Danish.

  PMID: 26651552 BACKGROUND

• Isaac L. Clonidine in the central nervous system: site and mechanism of hypotensive action. J Cardiovasc Pharmacol. 1980;2 Suppl 1:S5-19.

  PMID: 6154837 BACKGROUND

• Ydemann M, Nielsen BN, Wetterslev J, Henneberg S, Lauritsen T, Steen N, Edstrom B, Afshari A. Effect of clonidine to prevent agitation in children after sevoflurane anaesthesia: a randomised placebo controlled multicentre trial. Dan Med J. 2016 Jun;63(6):A5234.

  PMID: 27264945 BACKGROUND

• Lambert P, Cyna AM, Knight N, Middleton P. Clonidine premedication for postoperative analgesia in children. Cochrane Database Syst Rev. 2014 Jan 28;2014(1):CD009633. doi: 10.1002/14651858.CD009633.pub2.

  PMID: 24470114 BACKGROUND

• Boric K, Dosenovic S, Jelicic Kadic A, Batinic M, Cavar M, Urlic M, Markovina N, Puljak L. Interventions for postoperative pain in children: An overview of systematic reviews. Paediatr Anaesth. 2017 Sep;27(9):893-904. doi: 10.1111/pan.13203. Epub 2017 Jul 14.

  PMID: 28707454 BACKGROUND

• Wang W, Huang P, Gao W, Cao F, Yi M, Chen L, Guo X. Efficacy and Acceptability of Different Auxiliary Drugs in Pediatric Sevoflurane Anesthesia: A Network Meta-analysis of Mixed Treatment Comparisons. Sci Rep. 2016 Nov 10;6:36553. doi: 10.1038/srep36553.

  PMID: 27830713 BACKGROUND

• Moore AD, Anghelescu DL. Emergence Delirium in Pediatric Anesthesia. Paediatr Drugs. 2017 Feb;19(1):11-20. doi: 10.1007/s40272-016-0201-5.

  PMID: 27798810 BACKGROUND

• Afshari A. Clonidine in pediatric anesthesia: the new panacea or a drug still looking for an indication? Curr Opin Anaesthesiol. 2019 Jun;32(3):327-333. doi: 10.1097/ACO.0000000000000724.

  PMID: 31045639 BACKGROUND

• Ydemann M, Nielsen BN, Henneberg S, Jakobsen JC, Wetterslev J, Lauritsen T, Steen N, Edstrom B, Afshari A; PREVENT AGITATION Research Group. Intraoperative clonidine for prevention of postoperative agitation in children anaesthetised with sevoflurane (PREVENT AGITATION): a randomised, placebo-controlled, double-blind trial. Lancet Child Adolesc Health. 2018 Jan;2(1):15-24. doi: 10.1016/S2352-4642(17)30127-X. Epub 2017 Nov 2.

  PMID: 30169192 BACKGROUND

• Khetani JD, Madadi P, Sommer DD, Reddy D, Sistonen J, Ross CJ, Carleton BC, Hayden MR, Koren G. Apnea and oxygen desaturations in children treated with opioids after adenotonsillectomy for obstructive sleep apnea syndrome: a prospective pilot study. Paediatr Drugs. 2012 Dec 1;14(6):411-5. doi: 10.2165/11633570-000000000-00000.

  PMID: 23013460 BACKGROUND

• Kelly LE, Sommer DD, Ramakrishna J, Hoffbauer S, Arbab-Tafti S, Reid D, Maclean J, Koren G. Morphine or Ibuprofen for post-tonsillectomy analgesia: a randomized trial. Pediatrics. 2015 Feb;135(2):307-13. doi: 10.1542/peds.2014-1906.

  PMID: 25624387 BACKGROUND

• Jay MA, Thomas BM, Nandi R, Howard RF. Higher risk of opioid-induced respiratory depression in children with neurodevelopmental disability: a retrospective cohort study of 12 904 patients. Br J Anaesth. 2017 Feb;118(2):239-246. doi: 10.1093/bja/aew403.

  PMID: 28100528 BACKGROUND

• Oderda GM, Senagore AJ, Morland K, Iqbal SU, Kugel M, Liu S, Habib AS. Opioid-related respiratory and gastrointestinal adverse events in patients with acute postoperative pain: prevalence, predictors, and burden. J Pain Palliat Care Pharmacother. 2019 Sep-Dec;33(3-4):82-97. doi: 10.1080/15360288.2019.1668902. Epub 2019 Oct 14.

  PMID: 31609155 BACKGROUND

• Berghmans JM, Poley MJ, van der Ende J, Weber F, Van de Velde M, Adriaenssens P, Himpe D, Verhulst FC, Utens E. A Visual Analog Scale to assess anxiety in children during anesthesia induction (VAS-I): Results supporting its validity in a sample of day care surgery patients. Paediatr Anaesth. 2017 Sep;27(9):955-961. doi: 10.1111/pan.13206. Epub 2017 Jul 14.

  PMID: 28707384 BACKGROUND

• Malviya S, Voepel-Lewis T, Burke C, Merkel S, Tait AR. The revised FLACC observational pain tool: improved reliability and validity for pain assessment in children with cognitive impairment. Paediatr Anaesth. 2006 Mar;16(3):258-65. doi: 10.1111/j.1460-9592.2005.01773.x.

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MeSH Terms

Conditions

Thumb deformity; Trigger Finger Disorder; Polydactyly; Clubfoot; Talipes; Tarsal Coalition; Flatfoot; Syndactyly; Foot Deformities; Subungual exostoses; Hand Deformities, Congenital

Interventions

Clonidine; Sodium Chloride

Condition Hierarchy (Ancestors)

Tendon Entrapment; Tendinopathy; Muscular Diseases; Musculoskeletal Diseases; Limb Deformities, Congenital; Musculoskeletal Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Foot Deformities, Acquired; Foot Deformities, Congenital; Lower Extremity Deformities, Congenital; Synostosis; Dysostoses; Bone Diseases, Developmental; Bone Diseases; Hand Deformities; Upper Extremity Deformities, Congenital

Intervention Hierarchy (Ancestors)

Imidazolines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Nicola G. Clausen, Ph.D.

  Department of Anaesthesiology and Intensive Care at Odense University Hospital

  PRINCIPAL INVESTIGATOR

• Tom G. Hansen, Ph.D.

  Department of Anaesthesiology and Intensive Care at Odense University Hospital

  STUDY DIRECTOR

Central Study Contacts

Nicola G. Clausen, Ph.D.

CONTACT

0045 65 41 25 47; nicola.groes.clausen2@rsyd.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: May 25, 2020
• First Posted: September 25, 2020
• Study Start: March 1, 2021
• Primary Completion: December 20, 2021
• Study Completion: January 1, 2022
• Last Updated: September 10, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)