Interaction Between Antiemetic Drugs and ParacetamolPhase 3ANPATHYNCT01679093
Antagonism Research Between Antiemetics Agents and Acetaminophen in Thyroidectomy's Post-operative Analgesia.
A Phase 3 study testing ondansetron, Droperidol and Dexamethasone in people with Interaction Between Antiemetic Drugs and Paracetamol, run by University Hospital, Lille at 1 site in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Interaction Between Antiemetic Drugs and Paracetamol
- What is being tested?
- ondansetron, Droperidol and Dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 1 siteFrance
- Study dates
- Jun 2009to Jun 2011
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 9Show fewer
- protocol not respected
- protocol refused by the patient
- intellectual handicap
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Antagonism Research Between Antiemetics Agents (Droperidol, Dexametasone, Ondansetron) and Acetaminophen in Thyroidectomy's Post-operative Analgesia.
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.
Read the detailed description
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.
- Being tested
- ondansetron, Droperidol, Dexamethasone
- Keywords
- postoperative analgesia, paracetamol, 5-HT3 antagonist, ondansetron, PainMatcher
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ondansetronDrug
ondansetron: 4 mg intravenous administration afer the induction of anesthesia.
DroperidolDrug
droperidol: 1.25 mg intravenous administration after the induction of anesthesia.
DexamethasoneDrug
dexametasone: 4 mg intravenous administration after the induction of anesthesia.
| Study group | Role | What they receive |
|---|---|---|
| ONDANSETRON (OS) | Active comparator | 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. Receives: Drug: ondansetron |
| DROPERIDOL (DRO) | Active comparator | patients receiving droperidol at the beginning of the surgery to prevent PONV; and paracetamol at the end of the surgey for postoperative analgesia. Receives: Drug: Droperidol |
| DEXAMETHASONE (DEXA) | Active comparator | patients receiving dexamethasone at the beginning of the surgery to prevent PONV; and paracetamol at the end of the surgey for postoperative analgesia. Receives: Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
"electric nociception threshold" measured by PainMatcher
The PainMatcher is a pain self-assessment device using the electric stimulation of the median nerve. The patient maintains a pressure on an electrode box between the thumb and the index finger, creating a current of increasing intensity. The threshold of pain sensation is obtained when the patient releases his fingers from the electrode box. So whe raise the electric nociceptive threshold showned by the PainMatcher. We realize two measures and consider the second one.
objective measure.
Measured: during 2 hours after thyroidectomy in the postoperative care unit
Secondary outcomes (3)
numeric rating scale score
to evaluate the sensation of pain with a 11 levels going from 0 ( no pain) to 10 ( worst pain imaginable).
subjective measure.
Measured: during 2 hours after thyroidectomy in the postoperative care unit
need in rescue analgesia with nefopam in case of numeric rating scale score > 4
Measured: during 2 hours after thyroidectomy in the postoperative care unit
presence of postoperative nausea and vomiting
Measured: during the 2 hours after thyroidectomy in the postoperative care unit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2012 (estimated)
- Study startJun 2009
- Primary completionJan 2011
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Interaction Between Antiemetic Drugs and ParacetamolStudies of the same condition, open and under way.
- More trials run by University Hospital, LilleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Lille
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gilles Lebuffe, MD,PhD, Principal investigator, University hospital of Lille
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01679093
- Sponsor's protocol ID
- 2008-002701-40
- Other IDs
- 2008
- Acronym
- ANPATHY
- Status last verified
- Oct 2016
- First submitted
- 31 Aug 2012
- Last updated
- 27 Oct 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 16580905Girard 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.
PubMed 19270466Courade 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.
PubMed 11734181Pickering 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.
PubMed 17957182Apfel 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.
PubMed 15190136Apfel 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.
PubMed 15731931Kaiser 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.
PubMed 12065557Nielsen 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.
PubMed 18782884Candiotti 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.
PubMed 15731591Pelissier 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.
PubMed 7579145Pelissier 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.
PubMed 8764329Alloui 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.
PubMed 12044794Lund I, Lundeberg T, Kowalski J, Sandberg L, Budh CN, Svensson E. Evaluation of variations in sensory and pain threshold assessments by electrocutaneous stimulation. Physiother Theory Pract. 2005 Apr-Jun;21(2):81-92. doi: 10.1080/09593980590922307.
PubMed 16392461Nielsen 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.
PubMed 17430320Fujii 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.
PubMed 17275553
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Antagonism Research Between Antiemetics Agents (Droperidol, Dexametasone, Ondansetron) and Acetaminophen in Thyroidectomy's Post-operative Analgesia.
- ClinicalTrials.gov ID
- NCT01679093
- Acronym / sponsor ID
- ANPATHY / 2008-002701-40
- Keywords
- postoperative analgesia, paracetamol, 5-HT3 antagonist, ondansetron, PainMatcher
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- University Hospital, LilleUniversity, hospital or other
- Study start
- Jun 2009
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 5 Sep 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ONDANSETRON (OS) | Active comparator | Drug: ondansetronpatients 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. |
| DROPERIDOL (DRO) | Active comparator | Drug: Droperidolpatients receiving droperidol at the beginning of the surgery to prevent PONV; and paracetamol at the end of the surgey for postoperative analgesia. |
| DEXAMETHASONE (DEXA) | Active comparator | Drug: Dexamethasonepatients receiving dexamethasone at the beginning of the surgery to prevent PONV; and paracetamol at the end of the surgey for postoperative analgesia. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ondansetronondansetron: 4 mg intravenous administration afer the induction of anesthesia. | Drug | ONDANSETRON (OS) |
| Droperidoldroperidol: 1.25 mg intravenous administration after the induction of anesthesia. | Drug | DROPERIDOL (DRO) |
| Dexamethasonedexametasone: 4 mg intravenous administration after the induction of anesthesia. | Drug | DEXAMETHASONE (DEXA) |
Primary outcome
"electric nociception threshold" measured by PainMatcher
Time frame: during 2 hours after thyroidectomy in the postoperative care unit
The PainMatcher is a pain self-assessment device using the electric stimulation of the median nerve. The patient maintains a pressure on an electrode box between the thumb and the index finger, creating a current of increasing intensity. The threshold of pain sensation is obtained when the patient releases his fingers from the electrode box. So whe raise the electric nociceptive threshold showned by the PainMatcher. We realize two measures and consider the second one. objective measure.
3 secondary outcomes
numeric rating scale score
Time frame: during 2 hours after thyroidectomy in the postoperative care unit
need in rescue analgesia with nefopam in case of numeric rating scale score > 4
Time frame: during 2 hours after thyroidectomy in the postoperative care unit
presence of postoperative nausea and vomiting
Time frame: during the 2 hours after thyroidectomy in the postoperative care unit
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2016.
- Background: PubMed 16580905Pickering 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.
- Background: PubMed 19270466Girard 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.
- Background: PubMed 11734181Courade 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.
- Background: PubMed 17957182Pickering 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.
- Background: PubMed 15190136Apfel 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.
- Background: PubMed 15731931Apfel 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.
- Background: PubMed 12065557Kaiser 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.
- Background: PubMed 18782884Nielsen 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.
- Background: PubMed 15731591Candiotti 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.
- Background: PubMed 7579145Pelissier 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.
- Background: PubMed 8764329Pelissier 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.
- Background: PubMed 12044794Alloui 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.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gilles Lebuffe, MD,PhD principal investigator
University hospital of Lille
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ondansetron, Droperidol and Dexamethasone in people with Interaction Between Antiemetic Drugs and Paracetamol, run by University Hospital, Lille at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
"electric nociception threshold" measured by PainMatcher (time frame: during 2 hours after thyroidectomy in the postoperative care unit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01679093, which also lists 19 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2016; AzTrials last refreshed its copy on 6 Nov 2026.