Postoperative PainPhase 1NCT05943613
Efficacy of Intrathecal Clonidine Versus Neostigmine as Adjuvants to Bupivacaine on Postoperative Maternal and Fetal Outcomes After Elective Cesarean Section
A Phase 1 study testing Clonidine in people with Postoperative Pain, run by Assiut University.
Trial summary
The delivery of the infant into the arms of a conscious and pain free mother is one of the most exciting and rewarding moments in medicine. Neuraxial anesthesia is now the preferred technique for lower segment cesarean sections (LSCS). Read more about this study
- Who is it for?
- Ages 20 to 35 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Postoperative Pain
- What is being tested?
- Clonidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 111 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2023to 30 Nov 2025
- Phase
- Phase 1
- 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 20 to 35 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age: ranges from 20 - 35 years old.
- ASA physical status II.
- Singleton fetus at term.
- Parturient scheduled for elective lower segment cesarian section under spinal anethesia
Who cannot join
- Patient refusal.
- Contraindications to spinal blockade, such cardiorespiratory problems, coagulopathy, neurological disease, psychological troubles, and allergy to the used drugs.
- Morbid obesity.
- Failure of spinal blockade.
- Emergency CS.
- Complicated pregnancy.
- Intrauterine fetal compromise.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Efficacy of Intrathecal Clonidine Versus Neostigmine as Adjuvants to Bupivacaine on Postoperative Maternal and Fetal Outcomes After Elective Cesarean Section: A Randomized Double Blind Controlled Trial
The delivery of the infant into the arms of a conscious and pain free mother is one of the most exciting and rewarding moments in medicine. Neuraxial anesthesia is now the preferred technique for lower segment cesarean sections (LSCS). Although epidural, spinal, continuous spinal, and combined spinal-epidural techniques have all been advocated, most cesarean sections are performed under single-shot spinal anesthesia.
Even when a long acting local anesthetic like bupivacaine is used, the duration of spinal anesthesia (SA) is short and higher doses of analgesics are required in the postoperative period. Therefore, achieving a subarachnoid block that provides high quality postoperative analgesia of consistently prolonged duration is an attractive goal.
Read the detailed description
Opioids such as morphine, fentanyl, and sufentanil have been administered intrathecally as adjuvants to increase the duration of postoperative analgesia. Although they ensure superior quality of analgesia, they are associated with many side effects such as pruritus, nausea, vomiting, urinary retention, and especially late and unpredictable respiratory depression.
This has directed the research toward the use of newer and better local anesthetic additives for SA such as neostigmine, ketamine, midazolam, and clonidine.
Neostigmine is an anticholinesterase agent which increases the acetylcholine (Ach) concentration at the cholinergic synapse by blocking the activity of true and pseudocholinesterase enzymes. In postoperative period descending noradrenergic or cholinergic antinociceptive spinal system is activated by ongoing pain causing an increase in the release of Ach, which in the presence of neostigmine results in augmented analgesia. It has no untoward side effects such as respiratory depression, pruritus, and drowsiness as experienced with intrathecal narcotics.Clonidine is an α2-receptor agonist which has gained popularity in recent times as an adjuvant in spinal anesthesia. Analgesic effect of clonidine mediated by α2-adrenoceptors situated in the dorsal horn of spinal cord. The antinociceptive properties of clonidine indicate that it might be useful as an alternative to intrathecal opioids for postoperative analgesia, thus also avoiding the adverse effect of opioids.
Neostigmine was used in different dose ranges from 5 µg to 750 µg intrathecally but a low dose of 5 µg is sufficient to cause early onset of sensory and motor block.
On the other hand, clonidine was used in different doses from 15 µg to 450 µg, and many previous studies concluded that minimum 30 µg dose of clonidine provide a significant increase in the duration of sensory block, motor block, and spinal analgesia without increasing the incidence of side effects.
Dextrose 5% is used to make the adjuvant solutions more hyperbaric because in some studies, when hyperbaric solution of neostigmine was used, the incidence of nausea and vomiting was reduced by preventing cephalic spread of the drug to the brain stem.
Stress responses to surgical trauma and postoperative pain elicit diffuse changes in hormonal secretion such as adrenocorticotropic hormone (ACTH), cortisol and prolactin, with several deleterious metabolic and cardiovascular effects that can be prevented by effective postoperative analgesia.
Cortisol is a key player in the stress response and its secretion is facilitated by the ACTH which interacts with the sympathetic nervous system and the inhibitory control of endogenous opioid peptides, influencing pain processing.(12) Negative associations between cortisol levels and subsequent pain perception suggest the possibility that the hypothalamic-pituitary- adrenal (HPA) axis contributes to attenuating pain perception during acute stressful events, possibly mediated by increased cortisol.
- Conditions
- Postoperative Pain
- Being tested
- Clonidine
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClonidineDrug
compare the effect of intrathecal Clonidine and Neostigmine as adjuvants to Bupivacaine in elective cesarean section
| Study group | Role | What they receive |
|---|---|---|
| Group B | Placebo comparator | control group : will receive 2 ml (10 mg) of intrathecal hyperbaric Bupivacaine (0.5%) and another syringe containing 1 ml of Dextrose 5%. Receives: Drug: Clonidine |
| Group BC | Active comparator | will receive 2 ml (10 mg) of intrathecal hyperbaric Bupivacaine (0.5%) and another syringe containing Clonidine (30 µg) diluted in Dextrose 5% to a total volume of 1 ml. Receives: Drug: Clonidine |
| Group BN | Active comparator | will receive 2 ml (10 mg) of intrathecal hyperbaric Bupivacaine (0.5%) and another syringe containing Neostigmine (10 µg) diluted in Dextrose 5% to a total volume of 1 ml. Receives: Drug: Clonidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
postoperative analgesic efficacy of intrathecal clonidine and neostigmine by use of numerical rating scale (NRS) pain score.
using numerical rating scale (NRS) pain score that ranges from 0 indicating no pain up to 10 indicating the worst pain
Measured: 2 hours after time of sensory block
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2023
- Study start1 Dec 2023 (estimated)
- Primary completion30 Sep 2025 (estimated)
- Study completion30 Nov 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Postoperative PainStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe 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 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 111 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yasser Mamdouh Hassan Badawy, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05943613
- Sponsor's protocol ID
- Clonidine versus Neostigmine
- Status last verified
- Jul 2023
- First submitted
- 7 Jun 2023
- Last updated
- 13 Jul 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Intrathecal Clonidine Versus Neostigmine as Adjuvants to Bupivacaine on Postoperative Maternal and Fetal Outcomes After Elective Cesarean Section: A Randomized Double Blind Controlled Trial
- ClinicalTrials.gov ID
- NCT05943613
- Acronym / sponsor ID
- Clonidine versus Neostigmine
- Conditions
- Postoperative Pain
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 111 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Dec 2023 (estimated)
- Primary completion
- 30 Sep 2025 (estimated)
- Study completion
- 30 Nov 2025 (estimated)
- First posted
- 13 Jul 2023 (actual)
- 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 delivery of the infant into the arms of a conscious and pain free mother is one of the most exciting and rewarding moments in medicine. Neuraxial anesthesia is now the preferred technique for lower segment cesarean sections (LSCS). Although epidural, spinal, continuous spinal, and combined spinal-epidural techniques have all been advocated, most cesarean sections are performed under single-shot spinal anesthesia.
Even when a long acting local anesthetic like bupivacaine is used, the duration of spinal anesthesia (SA) is short and higher doses of analgesics are required in the postoperative period. Therefore, achieving a subarachnoid block that provides high quality postoperative analgesia of consistently prolonged duration is an attractive goal.
Detailed description
Opioids such as morphine, fentanyl, and sufentanil have been administered intrathecally as adjuvants to increase the duration of postoperative analgesia. Although they ensure superior quality of analgesia, they are associated with many side effects such as pruritus, nausea, vomiting, urinary retention, and especially late and unpredictable respiratory depression.
This has directed the research toward the use of newer and better local anesthetic additives for SA such as neostigmine, ketamine, midazolam, and clonidine.
Neostigmine is an anticholinesterase agent which increases the acetylcholine (Ach) concentration at the cholinergic synapse by blocking the activity of true and pseudocholinesterase enzymes. In postoperative period descending noradrenergic or cholinergic antinociceptive spinal system is activated by ongoing pain causing an increase in the release of Ach, which in the presence of neostigmine results in augmented analgesia. It has no untoward side effects such as respiratory depression, pruritus, and drowsiness as experienced with intrathecal narcotics.Clonidine is an α2-receptor agonist which has gained popularity in recent times as an adjuvant in spinal anesthesia. Analgesic effect of clonidine mediated by α2-adrenoceptors situated in the dorsal horn of spinal cord. The antinociceptive properties of clonidine indicate that it might be useful as an alternative to intrathecal opioids for postoperative analgesia, thus also avoiding the adverse effect of opioids.
Neostigmine was used in different dose ranges from 5 µg to 750 µg intrathecally but a low dose of 5 µg is sufficient to cause early onset of sensory and motor block.
On the other hand, clonidine was used in different doses from 15 µg to 450 µg, and many previous studies concluded that minimum 30 µg dose of clonidine provide a significant increase in the duration of sensory block, motor block, and spinal analgesia without increasing the incidence of side effects.
Dextrose 5% is used to make the adjuvant solutions more hyperbaric because in some studies, when hyperbaric solution of neostigmine was used, the incidence of nausea and vomiting was reduced by preventing cephalic spread of the drug to the brain stem.
Stress responses to surgical trauma and postoperative pain elicit diffuse changes in hormonal secretion such as adrenocorticotropic hormone (ACTH), cortisol and prolactin, with several deleterious metabolic and cardiovascular effects that can be prevented by effective postoperative analgesia.
Cortisol is a key player in the stress response and its secretion is facilitated by the ACTH which interacts with the sympathetic nervous system and the inhibitory control of endogenous opioid peptides, influencing pain processing.(12) Negative associations between cortisol levels and subsequent pain perception suggest the possibility that the hypothalamic-pituitary- adrenal (HPA) axis contributes to attenuating pain perception during acute stressful events, possibly mediated by increased cortisol.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group B | Placebo comparator | Drug: Clonidinecontrol group : will receive 2 ml (10 mg) of intrathecal hyperbaric Bupivacaine (0.5%) and another syringe containing 1 ml of Dextrose 5%. |
| Group BC | Active comparator | Drug: Clonidinewill receive 2 ml (10 mg) of intrathecal hyperbaric Bupivacaine (0.5%) and another syringe containing Clonidine (30 µg) diluted in Dextrose 5% to a total volume of 1 ml. |
| Group BN | Active comparator | Drug: Clonidinewill receive 2 ml (10 mg) of intrathecal hyperbaric Bupivacaine (0.5%) and another syringe containing Neostigmine (10 µg) diluted in Dextrose 5% to a total volume of 1 ml. |
Who may qualify
- Ages
- 20 to 35 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Age: ranges from 20 - 35 years old.
- ASA physical status II.
- Singleton fetus at term.
- Parturient scheduled for elective lower segment cesarian section under spinal anethesia
Key exclusion criteria (7 listed)
- Patient refusal.
- Contraindications to spinal blockade, such cardiorespiratory problems, coagulopathy, neurological disease, psychological troubles, and allergy to the used drugs.
- Morbid obesity.
- Failure of spinal blockade.
- Emergency CS.
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 |
|---|---|---|
| Clonidinecompare the effect of intrathecal Clonidine and Neostigmine as adjuvants to Bupivacaine in elective cesarean section | Drug | Group B, Group BC, Group BN |
Primary outcome
postoperative analgesic efficacy of intrathecal clonidine and neostigmine by use of numerical rating scale (NRS) pain score.
Time frame: 2 hours after time of sensory block
using numerical rating scale (NRS) pain score that ranges from 0 indicating no pain up to 10 indicating the worst pain
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2023.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Clonidine in people with Postoperative Pain, run by Assiut University.
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 7 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: status not confirmed, as of the sponsor's last update on 13 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact yasser mamdouh hassan, assistant lecturer (01090433083, yassermamdouh486@aun.edu.eg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
postoperative analgesic efficacy of intrathecal clonidine and neostigmine by use of numerical rating scale (NRS) pain score. (time frame: 2 hours after time of sensory block). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Jul 2023.