Uncomplicated Singleton PregnanciesPhase 1NCT01719705
Effects of Pregabalin on Post-cesarean Pain
A Phase 1 study testing Pregabalin 300 mg group and Pregabalin 150 mg group in people with Uncomplicated Singleton Pregnancies, run by Mansoura University at 2 sites in Egypt.
Trial summary
Post-cesarean pain management is essential for early mobilization of the mother so that she becomes able to care of her newborn. There choices for postoperative analgesia include spinal, systemic, or both opioids, non-steroidal anti-inflammatory drugs (NSAIDs), local anesthetic infiltrations of the wound, or… Read more about this study
- Who is it for?
- Ages 18 to 38 years, women only
- Conditions the study is for
- Uncomplicated Singleton Pregnancies
- What is being tested?
- Pregabalin 300 mg group and Pregabalin 150 mg group
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 135 participants
- Where
- 2 sitesEgypt
- Study dates
- Nov 2012to Jun 2015
- 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 18 to 38 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- spinal anesthesia
- elective cesarean delivery
- breech presentation
- cephalopelvic disproportion
- previous caesarean delivery
- American Society of Anesthesiologists class I and II
Who cannot join
- communication barriers
- cardiovascular diseases
- renal diseases
- hepatic diseases
- endocrinal diseases
- neuropsychiatric diseases
Show all 22Show fewer
- morbid obesity
- diabetes mellitus
- anaemia
- bleeding disorders
- prolonged P-R interval
- hypersensitivity to pregabalin
- receiving pregabalin
- receiving anticonvulsants
- receiving antidepressants
- receiving antipsychotics
- alcohol or drug abuse
- Opiates abuse
- benzodiazepines during the last week
- pregnancy-induced hypertension
- evidence of intrauterine growth restriction
- fetal compromise
Trial locations and contacts
2 sites in 1 country.
Egypt2 sites
College of Medicine, Mansoura University
Al Mansurah, DK, 050
Mansoura University Hospitals
Al Mansurah, DK, 050
About this study
Official title: Efficacy of Preoperative Pregabalin on the Post-caesarean Pain; a Dose-response Study
Post-cesarean pain management is essential for early mobilization of the mother so that she becomes able to care of her newborn. There choices for postoperative analgesia include spinal, systemic, or both opioids, non-steroidal anti-inflammatory drugs (NSAIDs), local anesthetic infiltrations of the wound, or transverse abdominis plane blocks, which are determined by drug availability, regional and individual preferences, resource limitations and financial considerations. The use of opioids is associated with adverse effects such as nausea, pruritus, sedation, and occasionally respiratory depression.
Pregabalin is an anticonvulsant drug structurally related to the inhibitory neurotransmitter gamma amino butyric acid, that exerts its action by binding to the α-2-δ subunit of the voltage-dependent calcium channel. It reduces the release of the excitatory neurotransmitters and inhibits the hyperalgesia and central sensitization.
Read more
A recent meta-analysis demonstrated that pregabalin reduce the postoperative 24 hours cumulative opioid consumption and opioid-related adverse effects namely, vomiting and visual disturbances after surgery. Compared with the use of pregabalin doses lower than 300 mg, the use of doses higher than 300 mg even reduced opioid consumption by 35%.
It is not known if pregabalin is excreted in human milk. There is a case report on the extensive excretion of pregabalin in breast milk, but with low measured concentrations in infant as a consequence of maternal exposure during breast feeding. Food and Drug Administration recommends to discontinue nursing or to discontinue pregabalin in nursing mothers. Pre-delivery single exposure to pregabalin is expected to be safe for the newborns.
Up to the authors' best knowledge, this is the first clinical study on the efficacy and safety of the administration of pregabalin before cesarean delivery.
We hypothesis that the preoperative administration of a single dose of pregabalin will improve the quality of postoperative analgesia after cesarean delivery.
This placebo-controlled study aims to compare the effects of preoperative administrations of single oral doses of pregabalin 150 mg and 300 mg on the postoperative pain scores, cumulative patient controlled morphine consumptions, neonatal Apgar and neurologic and adaptive capacity scores (NACS), and maternal and neonatal adverse effects in parturients scheduled to elective Cesarean delivery under spinal anesthesia.
Read the detailed description
An independent investigator who will not be involved in the study will instruct the patients preoperatively about the use of patient controlled analgesia and visual analogue scale to assess the severity of postoperative pain (0 mm for no pain and100 mm for worst imaginable pain).
Anaesthetic management will be standardized. Oral ranitidine 150 mg and metoclopramide 10 mg will be given the night before and on the morning of surgery, with 0.3 mol/L sodium citrate 30 mL given 15 min before induction.
Ninety minutes before surgery, subjects will be allocated randomly into three groups by drawing sequentially numbered sealed opaque envelopes containing a software-generated randomization code to the placebo (n = 45), pregabalin 150 mg (n = 45) and the pregabalin 300 mg (n = 45) groups. The placebo and pregabalin capsules look identical and will be prepared by a local pharmacy. An anaesthesiologist not otherwise involved in the study and who will be blinded to treatment regimen will provide perioperative care. An independent investigator will collect perioperative data. All staff in the operating room will be unaware of patient allocation group.
Maternal monitoring will include electrocardiography, non-invasive blood pressure, and pulse oximetry. Left uterine displacement will be maintained.
Spinal anesthesia will be performed in all cases in sitting position at L3-L4 or L4-L5 spaces with hyperbaric bupivacaine 0.5% (12.5 mg) and fentanyl 20 µg. After the umbilical cord is clamped, a 10 IU infusion of oxytocin in 500 mL of lactated Ringer's solution will be infused.
A paediatrician blinded to study group allocation will record Apgar scores at 1 and 5 min, umbilical cord blood gas analysis and NACS at 15 min, 2h, 24 and 48 h after delivery. NACS gives a maximum of 40 with a score >35 denoting vigor.The percentage of infants scoring <35 will be determined.
Postoperative analgesic regime will be standardized in all patients with 12-hourly intramuscular diclofenac 75 mg started immediately at the end of surgery and morphine via patient-controlled analgesia (PCA): 1 mg bolus with an 8 minutes lockout. Postoperative nausea or vomiting will be treated with intravenous metoclopramide 10 mg as required.
Statistical analysis:
Based on a previous study,7 the mean postoperative cumulative morphine consumption at 24 h after caesarean delivery was 38 mg with a standard deviation of 14 mg. An a priori power analysis indicated that 45 subjects were required in each group to detect a 25% reduction in the cumulative morphine consumption at 24 h after caesarean delivery, that was assumed to have a clinically significant effect, with a type-I error of 0.0167 (0.05/3 possible comparisons) and a power of 90%. Additional patients (10%) were included for a final sample size of 150 patients to account for patient dropout during the course of the study.
- Conditions
- Uncomplicated Singleton Pregnancies
- Being tested
- Placebo, Pregabalin 300 mg group, Pregabalin 150 mg group
- Keywords
- caesarean delivery, spinal anesthesia, pregabalin, postoperative pain, morphine
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Ninety minutes before surgery, the parturients receive two identical placebo capsules
Pregabalin 300 mg groupDrug
Ninety minutes before surgery, the parturients receive two capsules of pregabalin 150 mg
Pregabalin 150 mg groupDrug
Ninety minutes before surgery, the parturients receive one capsule of pregabalin 150 mg and one placebo capsule
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | receive two identical placebo capsules Receives: Drug: Placebo |
| Pregabalin 150 mg group | Active comparator | one capsule of pregabalin 150 mg Receives: Drug: Pregabalin 150 mg group |
| Pregabalin 300 mg group | Active comparator | two capsules of pregabalin 150 mg Receives: Drug: Pregabalin 300 mg group |
What is being measured
The primary outcome is the main question the study is designed to answer.
cumulative patient controlled morphine consumptions
cumulative patient controlled morphine consumptions 24 hours after delivery
Measured: 24 hours after delivery
Secondary outcomes (5)
postoperative pain scores
visual analogue scale to assess the severity of postoperative pain (0 mm for no pain and100 mm for worst imaginable pain) at rest and on movement
Measured: 1, 4, 6, 12, 24 and 48 hours after delivery
neonatal Apgar scores
Measured: 1 and 5 min aftr delivery
Neurologic and adaptive capacity scores
NACS gives a maximum of 40 with a score >35 denoting vigor.The percentage of infants scoring <35 will be determined.
Measured: at 15 min, 2h, 24 and 48 h after delivery
Maternal sedation
sedation (0, alert; 1, somnolent easy to arouse; 2, somnolent difficult to arouse or asleep; 3, not arousable)
Measured: every two hours after delivery, for 48 hours after delivery
Maternal nausea and vomiting
nausea and vomiting (0: no nausea; 1: nausea no vomiting; 2: nausea and vomiting),
Measured: at 24 hours after delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2012 (estimated)
- Study startNov 2012
- Primary completionMay 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Uncomplicated Singleton PregnanciesStudies of the same condition, open and under way.
- More trials run by Mansoura 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 135 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mansoura University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mohamed R El Tahan, Mansoura University
- Investigators
- Samah A El Kenany, MD, Principal investigator, Anethesiology Dept, College of Medicine, Mansoura UniversityMohamed R El Tahan, M.D., Study chair, Mansoura University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01719705
- Sponsor's protocol ID
- R/60
- Status last verified
- Jul 2015
- First submitted
- 28 Oct 2012
- Last updated
- 31 Jul 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Preoperative Pregabalin on the Post-caesarean Pain; a Dose-response Study
- ClinicalTrials.gov ID
- NCT01719705
- Acronym / sponsor ID
- R/60
- Conditions
- Uncomplicated Singleton Pregnancies
- Keywords
- caesarean delivery, spinal anesthesia, pregabalin, postoperative pain, morphine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 135 participants (actual)
- Lead sponsor
- Mansoura UniversityUniversity, hospital or other
- Study start
- Nov 2012
- Primary completion
- May 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 1 Nov 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.
Post-cesarean pain management is essential for early mobilization of the mother so that she becomes able to care of her newborn. There choices for postoperative analgesia include spinal, systemic, or both opioids, non-steroidal anti-inflammatory drugs (NSAIDs), local anesthetic infiltrations of the wound, or transverse abdominis plane blocks, which are determined by drug availability, regional and individual preferences, resource limitations and financial considerations. The use of opioids is associated with adverse effects such as nausea, pruritus, sedation, and occasionally respiratory depression.
Pregabalin is an anticonvulsant drug structurally related to the inhibitory neurotransmitter gamma amino butyric acid, that exerts its action by binding to the α-2-δ subunit of the voltage-dependent calcium channel. It reduces the release of the excitatory neurotransmitters and inhibits the hyperalgesia and central sensitization.
A recent meta-analysis demonstrated that pregabalin reduce the postoperative 24 hours cumulative opioid consumption and opioid-related adverse effects namely, vomiting and visual disturbances after surgery. Compared with the use of pregabalin doses lower than 300 mg, the use of doses higher than 300 mg even reduced opioid consumption by 35%.
It is not known if pregabalin is excreted in human milk. There is a case report on the extensive excretion of pregabalin in breast milk, but with low measured concentrations in infant as a consequence of maternal exposure during breast feeding. Food and Drug Administration recommends to discontinue nursing or to discontinue pregabalin in nursing mothers. Pre-delivery single exposure to pregabalin is expected to be safe for the newborns.
Up to the authors' best knowledge, this is the first clinical study on the efficacy and safety of the administration of pregabalin before cesarean delivery.
We hypothesis that the preoperative administration of a single dose of pregabalin will improve the quality of postoperative analgesia after cesarean delivery.
This placebo-controlled study aims to compare the effects of preoperative administrations of single oral doses of pregabalin 150 mg and 300 mg on the postoperative pain scores, cumulative patient controlled morphine consumptions, neonatal Apgar and neurologic and adaptive capacity scores (NACS), and maternal and neonatal adverse effects in parturients scheduled to elective Cesarean delivery under spinal anesthesia.
Detailed description
An independent investigator who will not be involved in the study will instruct the patients preoperatively about the use of patient controlled analgesia and visual analogue scale to assess the severity of postoperative pain (0 mm for no pain and100 mm for worst imaginable pain).
Anaesthetic management will be standardized. Oral ranitidine 150 mg and metoclopramide 10 mg will be given the night before and on the morning of surgery, with 0.3 mol/L sodium citrate 30 mL given 15 min before induction.
Ninety minutes before surgery, subjects will be allocated randomly into three groups by drawing sequentially numbered sealed opaque envelopes containing a software-generated randomization code to the placebo (n = 45), pregabalin 150 mg (n = 45) and the pregabalin 300 mg (n = 45) groups. The placebo and pregabalin capsules look identical and will be prepared by a local pharmacy. An anaesthesiologist not otherwise involved in the study and who will be blinded to treatment regimen will provide perioperative care. An independent investigator will collect perioperative data. All staff in the operating room will be unaware of patient allocation group.
Maternal monitoring will include electrocardiography, non-invasive blood pressure, and pulse oximetry. Left uterine displacement will be maintained.
Spinal anesthesia will be performed in all cases in sitting position at L3-L4 or L4-L5 spaces with hyperbaric bupivacaine 0.5% (12.5 mg) and fentanyl 20 µg. After the umbilical cord is clamped, a 10 IU infusion of oxytocin in 500 mL of lactated Ringer's solution will be infused.
A paediatrician blinded to study group allocation will record Apgar scores at 1 and 5 min, umbilical cord blood gas analysis and NACS at 15 min, 2h, 24 and 48 h after delivery. NACS gives a maximum of 40 with a score >35 denoting vigor.The percentage of infants scoring <35 will be determined.
Postoperative analgesic regime will be standardized in all patients with 12-hourly intramuscular diclofenac 75 mg started immediately at the end of surgery and morphine via patient-controlled analgesia (PCA): 1 mg bolus with an 8 minutes lockout. Postoperative nausea or vomiting will be treated with intravenous metoclopramide 10 mg as required.
Statistical analysis:
Based on a previous study,7 the mean postoperative cumulative morphine consumption at 24 h after caesarean delivery was 38 mg with a standard deviation of 14 mg. An a priori power analysis indicated that 45 subjects were required in each group to detect a 25% reduction in the cumulative morphine consumption at 24 h after caesarean delivery, that was assumed to have a clinically significant effect, with a type-I error of 0.0167 (0.05/3 possible comparisons) and a power of 90%. Additional patients (10%) were included for a final sample size of 150 patients to account for patient dropout during the course of the study.
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 |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placeboreceive two identical placebo capsules |
| Pregabalin 150 mg group | Active comparator | Drug: Pregabalin 150 mg groupone capsule of pregabalin 150 mg |
| Pregabalin 300 mg group | Active comparator | Drug: Pregabalin 300 mg grouptwo capsules of pregabalin 150 mg |
Who may qualify
- Ages
- 18 to 38 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- spinal anesthesia
- elective cesarean delivery
- breech presentation
- cephalopelvic disproportion
- previous caesarean delivery
Key exclusion criteria (22 listed)
- communication barriers
- cardiovascular diseases
- renal diseases
- hepatic diseases
- endocrinal diseases
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 |
|---|---|---|
| PlaceboNinety minutes before surgery, the parturients receive two identical placebo capsules | Drug | Placebo |
| Pregabalin 300 mg groupNinety minutes before surgery, the parturients receive two capsules of pregabalin 150 mg | Drug | Pregabalin 300 mg group |
| Pregabalin 150 mg groupNinety minutes before surgery, the parturients receive one capsule of pregabalin 150 mg and one placebo capsule | Drug | Pregabalin 150 mg group |
Primary outcome
cumulative patient controlled morphine consumptions
Time frame: 24 hours after delivery
cumulative patient controlled morphine consumptions 24 hours after delivery
5 secondary outcomes
postoperative pain scores
Time frame: 1, 4, 6, 12, 24 and 48 hours after delivery
neonatal Apgar scores
Time frame: 1 and 5 min aftr delivery
Neurologic and adaptive capacity scores
Time frame: at 15 min, 2h, 24 and 48 h after delivery
Maternal sedation
Time frame: every two hours after delivery, for 48 hours after delivery
Maternal nausea and vomiting
Time frame: at 24 hours after delivery
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 31 Jul 2015.
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.
Samah A El Kenany, MD principal investigator
Anethesiology Dept, College of Medicine, Mansoura University
Mohamed R El Tahan, M.D. study chair
Mansoura University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pregabalin 300 mg group and Pregabalin 150 mg group in people with Uncomplicated Singleton Pregnancies, run by Mansoura University at 2 sites 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 6 inclusion and 22 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 31 Jul 2015. 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 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.
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?
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?
cumulative patient controlled morphine consumptions (time frame: 24 hours after delivery). 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 31 Jul 2015.