Cesarean SectionPhase 4NCT00921102
Atropine to Prevent Nausea and Vomiting After Spinal Anesthesia for Caesarean Section
A Phase 4 study testing Bupivacaine, Morphine and Isotonic saline solution in people with Cesarean Section and Anesthesia,Spinal, run by University of Parma at 2 sites in Italy.
Trial summary
The aim of this study is to assess the efficacy of atropine in preventing nausea and vomiting after spinal anesthesia with local anesthetic and morphine for elective Caesarean section. Patients enrolling in the study will be assigned to one of three groups. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Cesarean Section, Anesthesia,Spinal, Postoperative Nausea and Vomiting
- What is being tested?
- Bupivacaine, Morphine and Isotonic saline solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 216 participants
- Where
- 2 sitesItaly
- Study dates
- May 2007to May 2008
- Phase
- Phase 4
- 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients scheduled for elective Cesarean section at up to 42 weeks and 2 days
- Patients in ASA Physical Status Class I or II
- Informed written consent to participation
- No known gestosis
Who cannot join
- Any known fetal pathology
- Indication to general anesthesia
- Known allergy to any of the study drugs
- Baseline bradycardia or any cardiovascular disease
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
University of Messina
Messina, ME, 98122
University and Hospital of Parma (Azienda Ospedaliero-Universitaria di Parma)
Parma, PR, 43126
About this study
Official title: Intrathecal Atropine to Prevent Nausea and Vomiting After Spinal Anesthesia With Morphine for Elective Caesarean Section: a Randomized Controlled Trial
The aim of this study is to assess the efficacy of atropine in preventing nausea and vomiting after spinal anesthesia with local anesthetic and morphine for elective Caesarean section.
Patients enrolling in the study will be assigned to one of three groups. One will receive a small dose of intrathecal atropine; another will receive small-dose intravenous atropine; the third group will receive placebo.
Read the detailed description
Intrathecal (IT) morphine grants effective, durable and safe analgesia after Caesarean section. The most common adverse effects after IT morphine are widespread pruritus and postoperative nausea and vomiting (PONV).
Postoperative nausea and vomiting is multifactorial in origin; in addition to general and pre-existing risk factors, such as elevated gonadotropin and progesterone serum levels, parturients undergoing Caesarean section are exposed to drug-induced, hemodynamic and surgical (manipulation of the uterus) stimuli.
Anticholinergic agents, and particularly scopolamine, have long been known to decrease opioid-related nausea and vomiting, although their narrow therapeutic range and inconvenient route of administration (typically transdermal) has limited their application. Anticholinergic agents are thought to act via inhibition of muscarinic receptors in several regions of the medulla oblongata, which are implicated with nausea and vomiting generation; in addition to the chemoceptor trigger zone, these receptors are particularly concentrated in, but not limited to the nucleus tractus solitarius. Cholinergic receptors have been typically associated with motion sickness, but cholinergic agonists such as neostigmine have been shown to increase the incidence of PONV, especially when injected intrathecally.
Anticholinergic agents with muscarinic selectivity may be effective in preventing and treating PONV. Intravenous (IV) administration of scopolamine or atropine, but not glycopyrrolate, reduces the incidence of PONV. Intuitively, as glycopyrrolate does not cross the blood-brain barrier, most postoperative anti-emetic effects of anticholinergic drugs should be mediated by central receptors.
Few studies have specifically evaluated the antiemetic effect of IV atropine after balanced general or opioid-based regional anesthesia, with conflicting results. Atropine may represent a valid alternative to scopolamine and its adverse effects; however, its apparent duration of action is "brief" (minutes to 1 hour) when administered IV.
After we became aware of several observations by Ramaioli and De Amici on the efficacy of small-dose intrathecal (IT) atropine for the treatment of PONV after IT morphine administration, we set out to investigate the use of this agent for prophylaxis of PONV in a high-risk population, such as patients receiving IT morphine for postoperative analgesia after elective Caesarean section.
- Being tested
- Bupivacaine, Morphine, Isotonic saline solution, Atropine
- Keywords
- Atropine, Morphine, Analgesics, Opioid, Antiemetics
- Medical subject headings
- Postoperative Nausea and Vomiting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BupivacaineDrug
Also called Local Anesthetic, Hyperbaric Bupivacaine, Marcain Heavy Injection
12.5 mg of a 5 mg/ml hyperbaric solution, intrathecally
MorphineDrug
200 µg of a 200 µg/ml solution, intrathecally
Isotonic saline solutionDrug
Also called Sodium chloride
0.9% NaCl solution
0.1 ml, intrathecally in group Control and IV Atropine
0.1 ml, intravenously in group Control and Intrathecal Atropine
AtropineDrug
100 µg of a 1 mg/ml preservative-free solution
- intrathecally in group Intrathecal Atropine
- intravenously in group IV Atropine
| Study group | Role | What they receive |
|---|---|---|
| Control | Placebo comparator | Patients in this group will receive both an intrathecal and intravenous injection of saline solution, as a placebo comparator. Receives: Drug: Bupivacaine; Drug: Morphine; Drug: Isotonic saline solution |
| Intrathecal Atropine | Experimental | Patients in this group will receive intrathecal atropine as a prophylactic antiemetic agent. They will also receive intravenous saline solution to maintain blinding. Receives: Drug: Bupivacaine; Drug: Morphine; Drug: Isotonic saline solution; Drug: Atropine |
| IV Atropine | Active comparator | Patients in this group will receive a small dose of atropine via the intravenous route to examine its possible antiemetic activity. They will also receive intravenous saline solution to maintain blinding. Receives: Drug: Bupivacaine; Drug: Morphine; Drug: Isotonic saline solution; Drug: Atropine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of postoperative nausea and vomiting (PONV) as expressed by at least one rating > 3 on a numerical rating scale (0-10).
Measured: 12 hours post-operatively
Secondary outcomes (3)
Incidence and prevalence of PONV up to 24 h postoperatively, expressed as both ratings on a numerical rating scale and as the area under the curve of these ratings over time.
Measured: Up to 24 h postoperatively
Incidence of atropine-related side effects such as xerostomia, anxiety, tachycardia.
Measured: Up to 24 h postoperatively
Postoperative pain expressed as time to first request for supplemental analgesia and as rating on a numerical rating scale.
Measured: Up to 24 h postoperatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2009 (estimated)
- Study startMay 2007
- Primary completionFeb 2008
- Study completionMay 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Cesarean SectionStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 216 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Parma
- Sponsor type
- University, hospital or other
- Investigators
- Guido Fanelli, MD, Study chair, University of ParmaAndrea Cornini, MD, Principal investigator, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00921102
- Sponsor's protocol ID
- ANEST-OST-01
- Status last verified
- Jun 2009
- First submitted
- 15 Jun 2009
- Last updated
- 16 Jun 2009
- Results posted
- No
- Data monitoring committee
- No
Publications
Ramaioli F, De Amici D. Central antiemetic effect of atropine: our personal experience. Can J Anaesth. 1996 Oct;43(10):1079. doi: 10.1007/BF03011915. No abstract available.
PubMed 8896865Salmenpera M, Kuoppamaki R, Salmenpera A. Do anticholinergic agents affect the occurrence of postanaesthetic nausea? Acta Anaesthesiol Scand. 1992 Jul;36(5):445-8. doi: 10.1111/j.1399-6576.1992.tb03494.x.
PubMed 1632167Moscovici R, Prego G, Schwartz M, Steinfeld O. Epidural scopolamine administration in preventing nausea after epidural morphine. J Clin Anesth. 1995 Sep;7(6):474-6. doi: 10.1016/0952-8180(95)00056-n.
PubMed 8534463Kotelko DM, Rottman RL, Wright WC, Stone JJ, Yamashiro AY, Rosenblatt RM. Transdermal scopolamine decreases nausea and vomiting following cesarean section in patients receiving epidural morphine. Anesthesiology. 1989 Nov;71(5):675-8. doi: 10.1097/00000542-198911000-00009.
PubMed 2817461Griffiths JD, Gyte GM, Popham PA, Williams K, Paranjothy S, Broughton HK, Brown HC, Thomas J. Interventions for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section. Cochrane Database Syst Rev. 2021 May 18;5(5):CD007579. doi: 10.1002/14651858.CD007579.pub3.
PubMed 34002866
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intrathecal Atropine to Prevent Nausea and Vomiting After Spinal Anesthesia With Morphine for Elective Caesarean Section: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT00921102
- Acronym / sponsor ID
- ANEST-OST-01
- Keywords
- Atropine, Morphine, Analgesics, Opioid, Antiemetics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 216 participants (actual)
- Lead sponsor
- University of ParmaUniversity, hospital or other
- Study start
- May 2007
- Primary completion
- Feb 2008 (actual)
- Study completion
- May 2008 (actual)
- First posted
- 16 Jun 2009 (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 aim of this study is to assess the efficacy of atropine in preventing nausea and vomiting after spinal anesthesia with local anesthetic and morphine for elective Caesarean section.
Patients enrolling in the study will be assigned to one of three groups. One will receive a small dose of intrathecal atropine; another will receive small-dose intravenous atropine; the third group will receive placebo.
Detailed description
Intrathecal (IT) morphine grants effective, durable and safe analgesia after Caesarean section. The most common adverse effects after IT morphine are widespread pruritus and postoperative nausea and vomiting (PONV).
Postoperative nausea and vomiting is multifactorial in origin; in addition to general and pre-existing risk factors, such as elevated gonadotropin and progesterone serum levels, parturients undergoing Caesarean section are exposed to drug-induced, hemodynamic and surgical (manipulation of the uterus) stimuli.
Anticholinergic agents, and particularly scopolamine, have long been known to decrease opioid-related nausea and vomiting, although their narrow therapeutic range and inconvenient route of administration (typically transdermal) has limited their application. Anticholinergic agents are thought to act via inhibition of muscarinic receptors in several regions of the medulla oblongata, which are implicated with nausea and vomiting generation; in addition to the chemoceptor trigger zone, these receptors are particularly concentrated in, but not limited to the nucleus tractus solitarius. Cholinergic receptors have been typically associated with motion sickness, but cholinergic agonists such as neostigmine have been shown to increase the incidence of PONV, especially when injected intrathecally.
Anticholinergic agents with muscarinic selectivity may be effective in preventing and treating PONV. Intravenous (IV) administration of scopolamine or atropine, but not glycopyrrolate, reduces the incidence of PONV. Intuitively, as glycopyrrolate does not cross the blood-brain barrier, most postoperative anti-emetic effects of anticholinergic drugs should be mediated by central receptors.
Few studies have specifically evaluated the antiemetic effect of IV atropine after balanced general or opioid-based regional anesthesia, with conflicting results. Atropine may represent a valid alternative to scopolamine and its adverse effects; however, its apparent duration of action is "brief" (minutes to 1 hour) when administered IV.
After we became aware of several observations by Ramaioli and De Amici on the efficacy of small-dose intrathecal (IT) atropine for the treatment of PONV after IT morphine administration, we set out to investigate the use of this agent for prophylaxis of PONV in a high-risk population, such as patients receiving IT morphine for postoperative analgesia after elective Caesarean section.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Control | Placebo comparator | Drug: Bupivacaine, Drug: Morphine, Drug: Isotonic saline solutionPatients in this group will receive both an intrathecal and intravenous injection of saline solution, as a placebo comparator. |
| Intrathecal Atropine | Experimental | Drug: Bupivacaine, Drug: Morphine, Drug: Isotonic saline solution, Drug: AtropinePatients in this group will receive intrathecal atropine as a prophylactic antiemetic agent. They will also receive intravenous saline solution to maintain blinding. |
| IV Atropine | Active comparator | Drug: Bupivacaine, Drug: Morphine, Drug: Isotonic saline solution, Drug: AtropinePatients in this group will receive a small dose of atropine via the intravenous route to examine its possible antiemetic activity. They will also receive intravenous saline solution to maintain blinding. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients scheduled for elective Cesarean section at up to 42 weeks and 2 days
- Patients in ASA Physical Status Class I or II
- Informed written consent to participation
- No known gestosis
Key exclusion criteria (4 listed)
- Any known fetal pathology
- Indication to general anesthesia
- Known allergy to any of the study drugs
- Baseline bradycardia or any cardiovascular disease
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 |
|---|---|---|
| BupivacaineAlso: Local Anesthetic, Hyperbaric Bupivacaine, Marcain Heavy Injection12.5 mg of a 5 mg/ml hyperbaric solution, intrathecally | Drug | Control, IV Atropine, Intrathecal Atropine |
| Morphine200 µg of a 200 µg/ml solution, intrathecally | Drug | Control, IV Atropine, Intrathecal Atropine |
| Isotonic saline solutionAlso: Sodium chloride0.9% NaCl solution 0.1 ml, intrathecally in group Control and IV Atropine 0.1 ml, intravenously in group Control and Intrathecal Atropine | Drug | Control, IV Atropine, Intrathecal Atropine |
| Atropine100 µg of a 1 mg/ml preservative-free solution * intrathecally in group Intrathecal Atropine * intravenously in group IV Atropine | Drug | IV Atropine, Intrathecal Atropine |
Primary outcome
Incidence of postoperative nausea and vomiting (PONV) as expressed by at least one rating > 3 on a numerical rating scale (0-10).
Time frame: 12 hours post-operatively
3 secondary outcomes
Incidence and prevalence of PONV up to 24 h postoperatively, expressed as both ratings on a numerical rating scale and as the area under the curve of these ratings over time.
Time frame: Up to 24 h postoperatively
Incidence of atropine-related side effects such as xerostomia, anxiety, tachycardia.
Time frame: Up to 24 h postoperatively
Postoperative pain expressed as time to first request for supplemental analgesia and as rating on a numerical rating scale.
Time frame: Up to 24 h postoperatively
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 16 Jun 2009.
- Background: PubMed 8896865Ramaioli F, De Amici D. Central antiemetic effect of atropine: our personal experience. Can J Anaesth. 1996 Oct;43(10):1079. doi: 10.1007/BF03011915. No abstract available.
- Background: PubMed 1632167Salmenpera M, Kuoppamaki R, Salmenpera A. Do anticholinergic agents affect the occurrence of postanaesthetic nausea? Acta Anaesthesiol Scand. 1992 Jul;36(5):445-8. doi: 10.1111/j.1399-6576.1992.tb03494.x.
- Background: PubMed 8534463Moscovici R, Prego G, Schwartz M, Steinfeld O. Epidural scopolamine administration in preventing nausea after epidural morphine. J Clin Anesth. 1995 Sep;7(6):474-6. doi: 10.1016/0952-8180(95)00056-n.
- Background: PubMed 2817461Kotelko DM, Rottman RL, Wright WC, Stone JJ, Yamashiro AY, Rosenblatt RM. Transdermal scopolamine decreases nausea and vomiting following cesarean section in patients receiving epidural morphine. Anesthesiology. 1989 Nov;71(5):675-8. doi: 10.1097/00000542-198911000-00009.
- Derived from this study: PubMed 34002866Griffiths JD, Gyte GM, Popham PA, Williams K, Paranjothy S, Broughton HK, Brown HC, Thomas J. Interventions for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section. Cochrane Database Syst Rev. 2021 May 18;5(5):CD007579. doi: 10.1002/14651858.CD007579.pub3.
Related trials for Cesarean Section
Not yet recruiting
Comparison of Effect of Two Different Doses of Intravenous Oxytocin on Patients Undergoing Elective Cesarean Section
Postpartum Hemorrhage, Uterine Atony
Not yet recruitingObservational study
Ultrasound Assessment Of Gastric Volume In Pregnant Women Undergoing Elective Cesarean Section
Gestational Diabetes Mellitus (GDM), Obstetric Anesthesia
Active, not recruitingPhase 4
Effect of Dexmedetomidine on Postoperative Pain in Spinal Anesthesia for Cesarean Section at Assuit University Hospital
Cesarean Section
Active, not recruiting
Implementation of a Disparities in Labor Outcomes Dashboard
Labor Induction, Cesarean Birth
RecruitingPhase 1
Ketamine Pharmacokinetics and Pharmacodynamics for Postpartum Depression and Pain After Cesarean Delivery
Pain, Postpartum Depression
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.
Guido Fanelli, MD study chair
University of Parma
Andrea Cornini, MD principal investigator
Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bupivacaine, Morphine and Isotonic saline solution in people with Cesarean Section and Anesthesia,Spinal, run by University of Parma at 2 sites in Italy.
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 4 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 16 Jun 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Incidence of postoperative nausea and vomiting (PONV) as expressed by at least one rating > 3 on a numerical rating scale (0-10). (time frame: 12 hours post-operatively). 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 NCT00921102, which also lists 5 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 16 Jun 2009.