Antagonism Research Between Antiemetics Agents and Acetaminophen in Thyroidectomy's Post-operative Analgesia.

NCT ID: NCT01679093

Last Updated: 2016-10-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

66 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-06-30

Study Completion Date

2011-06-30

Brief Summary

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The purpose of our study is to determine if there is an antagonism between drugs used in the prevention of postoperative nausea and vomiting (PONV) on the analgesia led by acetaminophen after thyroidectomy.

Detailed Description

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It was shown that there was an antagonism of the ondansetron on the analgesia led by acetaminophen in a model of nociception by electrical stimulation using the PainMatcher in healthy volunteers. Our study try to determinate if a such antagonism exist in clinical conditions : 66 patients with an Apfel-score II undergoing thyroidectomy were randomized in 3 equal groups. Each group received an antiemetic (ondansetron, droperidol or dexamethasone) at the begining of the intervention and paracetamol at the end of the intervention for the postoperative analgesia. During 2 hours in the postoperative unit, we raised : the electrical pain's threshold with the PainMatcher, the numeric pain intensity scale and the presence of nausea or vomiting. For each patients we determined the cytochrome P450 2D6 activity that should have been able to explain a diminution of ondansetron's efficiency. Paracetamol blood levels were also raised in the postoperative unit.

Conditions

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Interaction Between Antiemetic Drugs and Paracetamol

Keywords

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postoperative analgesia paracetamol 5-HT3 antagonist ondansetron PainMatcher

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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ONDANSETRON (OS)

patients receiving ondansetron at the beginning of the surgery to prevent postoperative nausea and vomiting (PONV); and paracetamol at the end of the surgery for postoperative analgesia.

Group Type ACTIVE_COMPARATOR

ondansetron

Intervention Type DRUG

ondansetron: 4 mg intravenous administration afer the induction of anesthesia.

DROPERIDOL (DRO)

patients receiving droperidol at the beginning of the surgery to prevent PONV; and paracetamol at the end of the surgey for postoperative analgesia.

Group Type ACTIVE_COMPARATOR

Droperidol

Intervention Type DRUG

droperidol: 1.25 mg intravenous administration after the induction of anesthesia.

DEXAMETHASONE (DEXA)

patients receiving dexamethasone at the beginning of the surgery to prevent PONV; and paracetamol at the end of the surgey for postoperative analgesia.

Group Type ACTIVE_COMPARATOR

Dexamethasone

Intervention Type DRUG

dexametasone: 4 mg intravenous administration after the induction of anesthesia.

Interventions

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ondansetron

ondansetron: 4 mg intravenous administration afer the induction of anesthesia.

Intervention Type DRUG

Droperidol

droperidol: 1.25 mg intravenous administration after the induction of anesthesia.

Intervention Type DRUG

Dexamethasone

dexametasone: 4 mg intravenous administration after the induction of anesthesia.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* patients undergoing thyroidectomy without lymph node dissection
* American Society of Anesthesiologists physical status from I to III
* Apfel-score equal to 2
* informed consent signed

Exclusion Criteria

* pregnant and breast-feeding women
* addictive disorders
* psychic diseases
* allergy or contra-indication to a drug used in the study
* presence of postoperative nausea or vomiting
* administration of glucocorticoid for protecting recurrent laryngeal nerve.
* protocol not respected
* protocol refused by the patient
* intellectual handicap
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Lille

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilles Lebuffe, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

University hospital of Lille

Locations

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Hôpital Claude Huriez, CHRU

Lille, , France

Site Status

Countries

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France

References

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Pickering G, Loriot MA, Libert F, Eschalier A, Beaune P, Dubray C. Analgesic effect of acetaminophen in humans: first evidence of a central serotonergic mechanism. Clin Pharmacol Ther. 2006 Apr;79(4):371-8. doi: 10.1016/j.clpt.2005.12.307.

Reference Type BACKGROUND
PMID: 16580905 (View on PubMed)

Girard P, Pansart Y, Coppe MC, Niedergang B, Gillardin JM. Modulation of paracetamol and nefopam antinociception by serotonin 5-HT(3) receptor antagonists in mice. Pharmacology. 2009;83(4):243-6. doi: 10.1159/000207448. Epub 2009 Mar 9.

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Courade JP, Chassaing C, Bardin L, Alloui A, Eschalier A. 5-HT receptor subtypes involved in the spinal antinociceptive effect of acetaminophen in rats. Eur J Pharmacol. 2001 Nov 30;432(1):1-7. doi: 10.1016/s0014-2999(01)01464-9.

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Pickering G, Esteve V, Loriot MA, Eschalier A, Dubray C. Acetaminophen reinforces descending inhibitory pain pathways. Clin Pharmacol Ther. 2008 Jul;84(1):47-51. doi: 10.1038/sj.clpt.6100403. Epub 2007 Oct 24.

Reference Type BACKGROUND
PMID: 17957182 (View on PubMed)

Apfel CC, Korttila K, Abdalla M, Kerger H, Turan A, Vedder I, Zernak C, Danner K, Jokela R, Pocock SJ, Trenkler S, Kredel M, Biedler A, Sessler DI, Roewer N; IMPACT Investigators. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med. 2004 Jun 10;350(24):2441-51. doi: 10.1056/NEJMoa032196.

Reference Type BACKGROUND
PMID: 15190136 (View on PubMed)

Apfel CC, Bacher A, Biedler A, Danner K, Danzeisen O, Eberhart LH, Forst H, Fritz G, Hergert M, Frings G, Goebel A, Hopf HB, Kerger H, Kranke P, Lange M, Mertzlufft F, Motsch J, Paura A, Roewer N, Schneider E, Stoecklein K, Wermelt J, Zernak C. [A factorial trial of six interventions for the prevention of postoperative nausea and vomiting]. Anaesthesist. 2005 Mar;54(3):201-9. doi: 10.1007/s00101-005-0803-8. German.

Reference Type BACKGROUND
PMID: 15731931 (View on PubMed)

Kaiser R, Sezer O, Papies A, Bauer S, Schelenz C, Tremblay PB, Possinger K, Roots I, Brockmoller J. Patient-tailored antiemetic treatment with 5-hydroxytryptamine type 3 receptor antagonists according to cytochrome P-450 2D6 genotypes. J Clin Oncol. 2002 Jun 15;20(12):2805-11. doi: 10.1200/JCO.2002.09.064.

Reference Type BACKGROUND
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Nielsen M, Olsen NV. Genetic polymorphisms in the cytochrome P450 system and efficacy of 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting. Br J Anaesth. 2008 Oct;101(4):441-5. doi: 10.1093/bja/aen246. No abstract available.

Reference Type BACKGROUND
PMID: 18782884 (View on PubMed)

Candiotti KA, Birnbach DJ, Lubarsky DA, Nhuch F, Kamat A, Koch WH, Nikoloff M, Wu L, Andrews D. The impact of pharmacogenomics on postoperative nausea and vomiting: do CYP2D6 allele copy number and polymorphisms affect the success or failure of ondansetron prophylaxis? Anesthesiology. 2005 Mar;102(3):543-9. doi: 10.1097/00000542-200503000-00011.

Reference Type BACKGROUND
PMID: 15731591 (View on PubMed)

Pelissier T, Alloui A, Paeile C, Eschalier A. Evidence of a central antinociceptive effect of paracetamol involving spinal 5HT3 receptors. Neuroreport. 1995 Jul 31;6(11):1546-8. doi: 10.1097/00001756-199507310-00020.

Reference Type BACKGROUND
PMID: 7579145 (View on PubMed)

Pelissier T, Alloui A, Caussade F, Dubray C, Cloarec A, Lavarenne J, Eschalier A. Paracetamol exerts a spinal antinociceptive effect involving an indirect interaction with 5-hydroxytryptamine3 receptors: in vivo and in vitro evidence. J Pharmacol Exp Ther. 1996 Jul;278(1):8-14.

Reference Type BACKGROUND
PMID: 8764329 (View on PubMed)

Alloui A, Chassaing C, Schmidt J, Ardid D, Dubray C, Cloarec A, Eschalier A. Paracetamol exerts a spinal, tropisetron-reversible, antinociceptive effect in an inflammatory pain model in rats. Eur J Pharmacol. 2002 May 17;443(1-3):71-7. doi: 10.1016/s0014-2999(02)01578-9.

Reference Type BACKGROUND
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Reference Type BACKGROUND
PMID: 16392461 (View on PubMed)

Nielsen PR, Norgaard L, Rasmussen LS, Kehlet H. Prediction of post-operative pain by an electrical pain stimulus. Acta Anaesthesiol Scand. 2007 May;51(5):582-6. doi: 10.1111/j.1399-6576.2007.01271.x.

Reference Type BACKGROUND
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Fujii Y, Nakayama M. Efficacy of dexamethasone for reducing postoperative nausea and vomiting and analgesic requirements after thyroidectomy. Otolaryngol Head Neck Surg. 2007 Feb;136(2):274-7. doi: 10.1016/j.otohns.2006.09.013.

Reference Type BACKGROUND
PMID: 17275553 (View on PubMed)

Samer CF, Piguet V, Dayer P, Desmeules JA. [Genetic polymorphism and drug interactions: their importance in the treatment of pain]. Can J Anaesth. 2005 Oct;52(8):806-21. doi: 10.1007/BF03021775. French.

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Lo Y, Chia YY, Liu K, Ko NH. Morphine sparing with droperidol in patient-controlled analgesia. J Clin Anesth. 2005 Jun;17(4):271-5. doi: 10.1016/j.jclinane.2004.08.010.

Reference Type BACKGROUND
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McCleane GJ, Suzuki R, Dickenson AH. Does a single intravenous injection of the 5HT3 receptor antagonist ondansetron have an analgesic effect in neuropathic pain? A double-blinded, placebo-controlled cross-over study. Anesth Analg. 2003 Nov;97(5):1474-1478. doi: 10.1213/01.ANE.0000085640.69855.51.

Reference Type BACKGROUND
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Andrieu G, Amrouni H, Robin E, Carnaille B, Wattier JM, Pattou F, Vallet B, Lebuffe G. Analgesic efficacy of bilateral superficial cervical plexus block administered before thyroid surgery under general anaesthesia. Br J Anaesth. 2007 Oct;99(4):561-6. doi: 10.1093/bja/aem230. Epub 2007 Aug 6.

Reference Type BACKGROUND
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Other Identifiers

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2008-002701-40

Identifier Type: -

Identifier Source: org_study_id