Pain, AcuteNCT04932083
Intrathecal Midazolam, Fentanyl and Nalbuphine as Adjuvants to Bupivacaine in Spinal Anesthesia for Cesarean Section
A study testing Bupivacaine, Fentanyl and Nalbuphine in people with Pain, Acute, run by Benha University at 1 site in Egypt.
Trial summary
The main limitations of spinal anesthesia are its short duration of action and do not provide prolonged postoperative analgesia when it is performed only with local anesthetics. Adding adjuvants drugs to intrathecal local anesthetics improves quality and duration of spinal blockade, and prolongs postoperative… Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Pain, Acute
- What is being tested?
- Bupivacaine, Fentanyl and Nalbuphine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteEgypt
- Study dates
- 20 Jun 2021to 24 Feb 2022
- Phase
- Interventional
- 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 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- ASA physical status I and ASA II
- Age from 18-40 years
- Scheduled to undergo elective cesarean section under spinal anesthesia.
Who cannot join
- ASA physical status III or IV patients.
- Patients refuse spinal anesthesia.
- Patients physically dependent on narcotics or benzodiazepine.
- Patients with history of drug allergy to one of used adjuvants.
- Patients with gross spinal abnormality, localized skin sepsis, hemorrhagic diathesis or neurological involvement/ diseases and any contraindication for spine.
- Patients who are unable to communicate.
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- Morbid obesity.
- Failure of spinal blockade.
- Complicated pregnancy.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Intrathecal Midazolam is a Comparable Alternative to Fentanyl and Nalbuphine as Adjuvant to Bupivacaine in Spinal Anesthesia for Elective Cesarean Section; a Randomized Controlled Double-blind Trial
The main limitations of spinal anesthesia are its short duration of action and do not provide prolonged postoperative analgesia when it is performed only with local anesthetics. Adding adjuvants drugs to intrathecal local anesthetics improves quality and duration of spinal blockade, and prolongs postoperative analgesia. It is also possible to reduce dose of local anesthetics, as well as total amount of systemic postoperative analgesics.
Read the detailed description
Several spinal adjuvants have been used to improve spinal anesthesia quality and to prolong postsurgical analgesia; Intrathecal opioids are the most commonly utilized. Intrathecal opioids cause analgesia by binding to opioid receptors in the dorsal horn of the spinal cord. They prolong the duration of analgesia and allow early ambulation of patients.
Fentanyl, a short-acting lipophilic opioid, is known to augment the quality of subarachnoid block in many studies. However, worrisome adverse effects such as pruritus, urinary retention, post-operative vomiting, and respiratory depression limit the use of opioids.
Nalbuphine is a synthetic opioid with mixed agonist antagonist effect. It binds to both mu- and kappa receptors; binding of nalbuphine to mu receptors competitively displaces other mu-agonists from these receptors without any agonist activity, therefore decreasing the side effects on mu agonist (nausea, vomiting, respiratory depression, urinary retention, pruritis, and prolonged sedation). While when binding to kappa receptors, nalbuphine has agonist effect (analgesic effect) through the kappa receptors distributed in the brain and spinal cord. There have been no documented studies of nalbuphine neurotoxicity.
Midazolam is a short acting benzodiazepine with anxiolytic, sedative, anticonvulsant and muscle relaxant effects, influencing GABA receptor and influence on neurons by entering chloride into them. It is water soluble in its acid formulation but is highly lipid soluble in vivo. It has been reported to have a spinally mediated anti-nociceptive effect. Previous studies have shown that intrathecal administration of midazolam added to bupivacaine improves the duration and quality of spinal anesthesia.
This study is carried out to evaluate and compare the effects of intrathecal midazolam (2 mg), fentanyl (25 micrograms) and nalbuphine (800 micrograms) as additives to intrathecal hyperbaric bupivacaine (0.5 %) with regards to: onset and duration of sensory block, onset and duration of motor block, duration of effective analgesia postoperative, side effects associated with the drug.
- Conditions
- Pain, Acute
- Being tested
- Bupivacaine, Fentanyl, Nalbuphine, Midazolam
- Medical subject headings
- Acute Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BupivacaineDrug
patients will be put in the sitting position and lean forward. After sterilization, Dural puncture will be performed at L4-L5 interspace or L3-L4 with a 25 gauge Quincke spinal needle.
patients will receive the local anesthetic dose of 0.5% heavy bupivacaine (12.5 mg) and 0.5 ml of sterile water will be added.
FentanylDrug
patients will be put in the sitting position and lean forward. After sterilization, Dural puncture will be performed at L4-L5 interspace or L3-L4 with a 25 gauge Quincke spinal needle.
patients will receive the local anesthetic dose of 0.5% heavy bupivacaine (12.5 mg) and 0.5 ml of fentanyl (25µg) will be added.
NalbuphineDrug
patients will be put in the sitting position and lean forward. After sterilization, Dural puncture will be performed at L4-L5 interspace or L3-L4 with a 25 gauge Quincke spinal needle.
patients will receive the local anesthetic dose of 0.5% heavy bupivacaine (12.5 mg) and 0.8 mg nalbuphine hydrochloride in 0.5 ml sterile water will be added.
MidazolamDrug
patients will be put in the sitting position and lean forward. After sterilization, Dural puncture will be performed at L4-L5 interspace or L3-L4 with a 25 gauge Quincke spinal needle.
patients will receive the local anesthetic dose of 0.5% heavy bupivacaine (12.5 mg) and 0.4 ml of midazolam (2mg) + 0.1 ml of sterile water will be added.
| Study group | Role | What they receive |
|---|---|---|
| Bupivacaine | Placebo comparator | patients will receive 2.5 ml of 0.5% hyperbaric bupivacaine (12.5 mg) plus 0.5 ml sterile water. Receives: Drug: Bupivacaine |
| Fentanyl | Experimental | patients will receive 2.5 ml of 0.5% hyperbaric bupivacaine (12.5 mg) plus 0.5 ml fentanyl (25µg). Receives: Drug: Fentanyl |
| Nalbuphine | Experimental | patients will receive 2.5 ml of 0.5% hyperbaric bupivacaine (12.5 mg) plus 0.8 mg nalbuphine hydrochloride in 0.5 ml sterile water. Receives: Drug: Nalbuphine |
| Midazolam | Experimental | patients will receive 2.5 ml of 0.5% hyperbaric bupivacaine (12.5 mg) plus 2mg of midazolam in 0.5 ml sterile water. Receives: Drug: Midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Duration of effective analgesia
it is the time interval from the subarachnoid block to the first analgesic intervention (VAS >3)
Measured: 24 hours postoperative
Secondary outcomes (6)
The onset of sensory block:
it is the time from end of intrathecal injection to absence of pain at T5 dermatome.
Measured: 2 minutes for ten minutes, every 5 minutes for the next 20 minutes after intrathecal injection
Duration of complete sensory block:
it is the time interval from the subarachnoid block to the first sensation of pain (VAS >0).
Measured: 12 hours postoperative
Onset of complete motor blockade
it is the time per minutes from intrathecal injection until Bromage scale to be 3.
Measured: every 2 minutes for 10 minutes after intrathecal injection
Duration of motor block:
it is the time per minutes from intrathecal injection until Bromage score 0.
Measured: 6 hours postoperative
Total dose of analgesic consumption
if VAS pain score >3, intravenous 30 mg keterolac will be administered and can be repeated after 6 h if needed. If the mother was still complaining of pain or the VAS is still greater than 3 after 20 min from ketorolac injection, she will be given intravenous pethidine in a dose of 0.5 mg/kg.
Measured: 24 hours postoperative
Maternal adverse effects
All mothers will be monitored for the associated adverse effects such as postoperative nausea and vomiting (PONV), sedation, pruritus, hypotension, bradycardia, shivering, and respiratory depression.
Measured: 24 hours postoperative
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2021
- Study start20 Jun 2021
- Primary completion14 Jan 2022
- Study completion24 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pain, AcuteStudies of the same condition, open and under way.
- More trials run by Benha 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Benha University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Samar Rafik Mohamed Amin, Benha University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04932083
- Sponsor's protocol ID
- RC6-5-2021
- Status last verified
- Mar 2022
- First submitted
- 14 Jun 2021
- Last updated
- 5 Apr 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intrathecal Midazolam is a Comparable Alternative to Fentanyl and Nalbuphine as Adjuvant to Bupivacaine in Spinal Anesthesia for Elective Cesarean Section; a Randomized Controlled Double-blind Trial
- ClinicalTrials.gov ID
- NCT04932083
- Acronym / sponsor ID
- RC6-5-2021
- Conditions
- Pain, Acute
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Benha UniversityUniversity, hospital or other
- Study start
- 20 Jun 2021 (actual)
- Primary completion
- 14 Jan 2022 (actual)
- Study completion
- 24 Feb 2022 (actual)
- First posted
- 18 Jun 2021 (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 main limitations of spinal anesthesia are its short duration of action and do not provide prolonged postoperative analgesia when it is performed only with local anesthetics. Adding adjuvants drugs to intrathecal local anesthetics improves quality and duration of spinal blockade, and prolongs postoperative analgesia. It is also possible to reduce dose of local anesthetics, as well as total amount of systemic postoperative analgesics.
Detailed description
Several spinal adjuvants have been used to improve spinal anesthesia quality and to prolong postsurgical analgesia; Intrathecal opioids are the most commonly utilized. Intrathecal opioids cause analgesia by binding to opioid receptors in the dorsal horn of the spinal cord. They prolong the duration of analgesia and allow early ambulation of patients.
Fentanyl, a short-acting lipophilic opioid, is known to augment the quality of subarachnoid block in many studies. However, worrisome adverse effects such as pruritus, urinary retention, post-operative vomiting, and respiratory depression limit the use of opioids.
Nalbuphine is a synthetic opioid with mixed agonist antagonist effect. It binds to both mu- and kappa receptors; binding of nalbuphine to mu receptors competitively displaces other mu-agonists from these receptors without any agonist activity, therefore decreasing the side effects on mu agonist (nausea, vomiting, respiratory depression, urinary retention, pruritis, and prolonged sedation). While when binding to kappa receptors, nalbuphine has agonist effect (analgesic effect) through the kappa receptors distributed in the brain and spinal cord. There have been no documented studies of nalbuphine neurotoxicity.
Midazolam is a short acting benzodiazepine with anxiolytic, sedative, anticonvulsant and muscle relaxant effects, influencing GABA receptor and influence on neurons by entering chloride into them. It is water soluble in its acid formulation but is highly lipid soluble in vivo. It has been reported to have a spinally mediated anti-nociceptive effect. Previous studies have shown that intrathecal administration of midazolam added to bupivacaine improves the duration and quality of spinal anesthesia.
This study is carried out to evaluate and compare the effects of intrathecal midazolam (2 mg), fentanyl (25 micrograms) and nalbuphine (800 micrograms) as additives to intrathecal hyperbaric bupivacaine (0.5 %) with regards to: onset and duration of sensory block, onset and duration of motor block, duration of effective analgesia postoperative, side effects associated with the drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Bupivacaine | Placebo comparator | Drug: Bupivacainepatients will receive 2.5 ml of 0.5% hyperbaric bupivacaine (12.5 mg) plus 0.5 ml sterile water. |
| Fentanyl | Experimental | Drug: Fentanylpatients will receive 2.5 ml of 0.5% hyperbaric bupivacaine (12.5 mg) plus 0.5 ml fentanyl (25µg). |
| Nalbuphine | Experimental | Drug: Nalbuphinepatients will receive 2.5 ml of 0.5% hyperbaric bupivacaine (12.5 mg) plus 0.8 mg nalbuphine hydrochloride in 0.5 ml sterile water. |
| Midazolam | Experimental | Drug: Midazolampatients will receive 2.5 ml of 0.5% hyperbaric bupivacaine (12.5 mg) plus 2mg of midazolam in 0.5 ml sterile water. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- ASA physical status I and ASA II
- Age from 18-40 years
- Scheduled to undergo elective cesarean section under spinal anesthesia.
Key exclusion criteria (9 listed)
- ASA physical status III or IV patients.
- Patients refuse spinal anesthesia.
- Patients physically dependent on narcotics or benzodiazepine.
- Patients with history of drug allergy to one of used adjuvants.
- Patients with gross spinal abnormality, localized skin sepsis, hemorrhagic diathesis or neurological involvement/ diseases and any contraindication for spine.
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 |
|---|---|---|
| Bupivacainepatients will be put in the sitting position and lean forward. After sterilization, Dural puncture will be performed at L4-L5 interspace or L3-L4 with a 25 gauge Quincke spinal needle. patients will receive the local anesthetic dose of 0.5% heavy bupivacaine (12.5 mg) and 0.5 ml of sterile water will be added. | Drug | Bupivacaine |
| Fentanylpatients will be put in the sitting position and lean forward. After sterilization, Dural puncture will be performed at L4-L5 interspace or L3-L4 with a 25 gauge Quincke spinal needle. patients will receive the local anesthetic dose of 0.5% heavy bupivacaine (12.5 mg) and 0.5 ml of fentanyl (25µg) will be added. | Drug | Fentanyl |
| Nalbuphinepatients will be put in the sitting position and lean forward. After sterilization, Dural puncture will be performed at L4-L5 interspace or L3-L4 with a 25 gauge Quincke spinal needle. patients will receive the local anesthetic dose of 0.5% heavy bupivacaine (12.5 mg) and 0.8 mg nalbuphine hydrochloride in 0.5 ml sterile water will be added. | Drug | Nalbuphine |
| Midazolampatients will be put in the sitting position and lean forward. After sterilization, Dural puncture will be performed at L4-L5 interspace or L3-L4 with a 25 gauge Quincke spinal needle. patients will receive the local anesthetic dose of 0.5% heavy bupivacaine (12.5 mg) and 0.4 ml of midazolam (2mg) + 0.1 ml of sterile water will be added. | Drug | Midazolam |
Primary outcome
Duration of effective analgesia
Time frame: 24 hours postoperative
it is the time interval from the subarachnoid block to the first analgesic intervention (VAS >3)
6 secondary outcomes
The onset of sensory block:
Time frame: 2 minutes for ten minutes, every 5 minutes for the next 20 minutes after intrathecal injection
Duration of complete sensory block:
Time frame: 12 hours postoperative
Onset of complete motor blockade
Time frame: every 2 minutes for 10 minutes after intrathecal injection
Duration of motor block:
Time frame: 6 hours postoperative
Total dose of analgesic consumption
Time frame: 24 hours postoperative
Maternal adverse effects
Time frame: 24 hours postoperative
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 5 Apr 2022.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Bupivacaine, Fentanyl and Nalbuphine in people with Pain, Acute, run by Benha University at 1 site in Egypt.
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 3 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 5 Apr 2022. 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 Egypt. 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.
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?
Duration of effective analgesia (time frame: 24 hours postoperative). 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 5 Apr 2022.