ShiveringPhase 4NCT07855523
Efficacy of Intravenous Midazolam-Ketamine Combination Versus Placebo for Prevention of Post-Spinal Shivering in Elective Cesarean Section
A Phase 4 study testing Midazolam and Ketamine and 0.9% Sodium Chloride in people with Shivering and Post-Spinal Shivering, run by Assiut University.
Trial summary
Spinal anesthesia is the preferred anesthetic method for elective cesarean deliveries, but it frequently causes post-spinal shivering. Shivering causes marked maternal discomfort, interferes with clinical monitoring, and increases oxygen consumption and metabolic workload. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Shivering, Post-Spinal Shivering, Hypothermia
- What is being tested?
- Midazolam and Ketamine and 0.9% Sodium Chloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- No sites listed yet
- Study dates
- Nov 2026to Dec 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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
- No healthy volunteers
- Adult
Who may be able to join
- Pregnant women aged 18 to 40 years old.
- American Society of Anesthesiologists (ASA) physical status I or II.
- Singleton pregnancy.
- Term pregnancy (37 to 41 weeks of gestation).
- Scheduled for elective cesarean section under spinal anesthesia.
Who cannot join
- Patient refusal.
- Body mass index (BMI) ≥ 40 kg/m².
- Contraindications to spinal anesthesia (e.g., coagulopathy, local infection at the puncture site).
- Known hypersensitivity or allergy to midazolam or ketamine.
- Pre-existing hypertension, pre-eclampsia, or cardiovascular disease.
- Severe cardiovascular, renal, or hepatic dysfunction.
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- Neurological or psychiatric disorders (including epilepsy or history of psychosis).
- Baseline (preoperative) body temperature < 36°C or > 37.5°C.
- Chronic use of sedatives, opioids, or medications affecting thermoregulation.
About this study
Official title: Efficacy of Intravenous Midazolam-Ketamine Combination Versus Placebo for Prevention of Post-Spinal Shivering in Elective Cesarean Section: A Randomized Controlled Trial
Spinal anesthesia is the preferred anesthetic method for elective cesarean deliveries, but it frequently causes post-spinal shivering. Shivering causes marked maternal discomfort, interferes with clinical monitoring, and increases oxygen consumption and metabolic workload.
This study aims to assess whether a prophylactic intravenous combination of low-dose midazolam and low-dose ketamine reduces the occurrence and severity of shivering compared with a placebo in women undergoing elective cesarean delivery under spinal anesthesia.
Read more
A total of 120 parturients will be randomly assigned into two equal groups:
- Combination Group: Receives intravenous midazolam (0.0375 mg/kg) combined with ketamine (0.25 mg/kg) diluted in 20 mL of 0.9% normal saline.
- Control Group: Receives 20 mL of 0.9% normal saline intravenously as a placebo.
In both groups, the intravenous infusion is administered over 10 minutes immediately following delivery of the infant and clamping of the umbilical cord, ensuring no transplacental transfer of the study medications to the newborn.
The primary objective is to evaluate the proportion of patients who develop shivering during the first 60 minutes after arrival in the post-anesthesia care unit (PACU). Secondary objectives include shivering severity, the requirement for rescue anti-shivering medication, intraoperative and postoperative sedation levels, hemodynamic stability, body temperature course, potential medication side effects, and maternal satisfaction.
- Conditions
- Shivering, Post-Spinal Shivering, Hypothermia, Cesarean Section
- Being tested
- Midazolam and Ketamine, 0.9% Sodium Chloride
- Keywords
- Midazolam, Ketamine, Spinal Anesthesia, Cesarean Delivery, Postanesthetic Shivering, Crossley and Mahajan Scale, Ramsay Sedation Scale
- Medical subject headings
- Hypothermia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Midazolam and KetamineDrug
Patients receive an intravenous infusion containing a combination of midazolam 0.0375 mg/kg (37.5 µg/kg) and ketamine 0.25 mg/kg diluted in 0.9% sodium chloride to a total volume of 20 mL. The infusion is administered over 10 minutes immediately after delivery of the infant and clamping of the umbilical cord.
0.9% Sodium ChlorideDrug
Patients receive 20 mL of 0.9% sodium chloride administered intravenously over 10 minutes immediately after delivery of the infant and clamping of the umbilical cord.
| Study group | Role | What they receive |
|---|---|---|
| Midazolam-Ketamine Combination Group | Experimental | Patients receive an intravenous infusion of midazolam 0.0375 mg/kg (37.5 µg/kg) combined with ketamine 0.25 mg/kg, diluted in 0.9% sodium chloride to a total volume of 20 mL, administered over 10 minutes immediately after fetal delivery and umbilical cord clamping. Receives: Drug: Midazolam and Ketamine |
| Placebo Control Group | Placebo comparator | Patients receive 20 mL of 0.9% sodium chloride intravenously over 10 minutes, administered immediately after fetal delivery and umbilical cord clamping. Receives: Drug: 0.9% Sodium Chloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Post-Spinal Shivering
Percentage of participants who develop shivering, defined as Grade 2 or higher (visible muscle activity) on the Crossley and Mahajan Shivering Scale.
Measured: Up to 60 minutes after arrival in the post-anesthesia care unit (PACU)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2026
- Study startNov 2026 (estimated)
- Primary completionNov 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ShiveringStudies 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Abdelrahman Mohamed Saad Mohamed, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07855523
- Sponsor's protocol ID
- Midazolam-Ketamine: Shivering
- Status last verified
- Sep 2026
- First submitted
- 28 Sep 2026
- Last updated
- 2 Oct 2026
- 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 2 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Intravenous Midazolam-Ketamine Combination Versus Placebo for Prevention of Post-Spinal Shivering in Elective Cesarean Section: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07855523
- Acronym / sponsor ID
- Midazolam-Ketamine: Shivering
- Conditions
- Shivering, Post-Spinal Shivering, Hypothermia, Cesarean Section
- Keywords
- Midazolam, Ketamine, Spinal Anesthesia, Cesarean Delivery, Postanesthetic Shivering, Crossley and Mahajan Scale, Ramsay Sedation Scale
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- Nov 2026 (estimated)
- Primary completion
- Nov 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 2 Oct 2026 (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.
Spinal anesthesia is the preferred anesthetic method for elective cesarean deliveries, but it frequently causes post-spinal shivering. Shivering causes marked maternal discomfort, interferes with clinical monitoring, and increases oxygen consumption and metabolic workload.
This study aims to assess whether a prophylactic intravenous combination of low-dose midazolam and low-dose ketamine reduces the occurrence and severity of shivering compared with a placebo in women undergoing elective cesarean delivery under spinal anesthesia.
A total of 120 parturients will be randomly assigned into two equal groups:
- Combination Group: Receives intravenous midazolam (0.0375 mg/kg) combined with ketamine (0.25 mg/kg) diluted in 20 mL of 0.9% normal saline.
- Control Group: Receives 20 mL of 0.9% normal saline intravenously as a placebo.
In both groups, the intravenous infusion is administered over 10 minutes immediately following delivery of the infant and clamping of the umbilical cord, ensuring no transplacental transfer of the study medications to the newborn.
The primary objective is to evaluate the proportion of patients who develop shivering during the first 60 minutes after arrival in the post-anesthesia care unit (PACU). Secondary objectives include shivering severity, the requirement for rescue anti-shivering medication, intraoperative and postoperative sedation levels, hemodynamic stability, body temperature course, potential medication side effects, and maternal satisfaction.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Midazolam-Ketamine Combination Group | Experimental | Drug: Midazolam and KetaminePatients receive an intravenous infusion of midazolam 0.0375 mg/kg (37.5 µg/kg) combined with ketamine 0.25 mg/kg, diluted in 0.9% sodium chloride to a total volume of 20 mL, administered over 10 minutes immediately after fetal delivery and umbilical cord clamping. |
| Placebo Control Group | Placebo comparator | Drug: 0.9% Sodium ChloridePatients receive 20 mL of 0.9% sodium chloride intravenously over 10 minutes, administered immediately after fetal delivery and umbilical cord clamping. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Pregnant women aged 18 to 40 years old.
- American Society of Anesthesiologists (ASA) physical status I or II.
- Singleton pregnancy.
- Term pregnancy (37 to 41 weeks of gestation).
- Scheduled for elective cesarean section under spinal anesthesia.
Key exclusion criteria (9 listed)
- Patient refusal.
- Body mass index (BMI) ≥ 40 kg/m².
- Contraindications to spinal anesthesia (e.g., coagulopathy, local infection at the puncture site).
- Known hypersensitivity or allergy to midazolam or ketamine.
- Pre-existing hypertension, pre-eclampsia, or 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 |
|---|---|---|
| Midazolam and KetaminePatients receive an intravenous infusion containing a combination of midazolam 0.0375 mg/kg (37.5 µg/kg) and ketamine 0.25 mg/kg diluted in 0.9% sodium chloride to a total volume of 20 mL. The infusion is administered over 10 minutes immediately after delivery of the infant and clamping of the umbilical cord. | Drug | Midazolam-Ketamine Combination Group |
| 0.9% Sodium ChloridePatients receive 20 mL of 0.9% sodium chloride administered intravenously over 10 minutes immediately after delivery of the infant and clamping of the umbilical cord. | Drug | Placebo Control Group |
Primary outcome
Percentage of Participants With Post-Spinal Shivering
Time frame: Up to 60 minutes after arrival in the post-anesthesia care unit (PACU)
Percentage of participants who develop shivering, defined as Grade 2 or higher (visible muscle activity) on the Crossley and Mahajan Shivering Scale.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2026.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Midazolam and Ketamine and 0.9% Sodium Chloride in people with Shivering and Post-Spinal Shivering, 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 5 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: opening soon, as of the sponsor's last update on 2 Oct 2026. 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 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?
This study is still under way. Results are not available in the source record yet.
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?
Percentage of Participants With Post-Spinal Shivering (time frame: Up to 60 minutes after arrival in the post-anesthesia care unit (PACU)). 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 2 Oct 2026.