Effects of Pregabalin on Post-cesarean Pain

This study is currently recruiting participants.
Verified November 2012 by Mansoura University
Sponsor:
Information provided by (Responsible Party):
Mohamed R El Tahan, Mansoura University
ClinicalTrials.gov Identifier:
NCT01719705
First received: October 28, 2012
Last updated: November 15, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Uncomplicated Singleton Pregnancies
Drug: Placebo
Drug: Pregabalin 300 mg group
Drug: Pregabalin 150 mg group
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy of Preoperative Pregabalin on the Post-caesarean Pain; a Dose-response Study

Resource links provided by NLM:


Further study details as provided by Mansoura University:

Primary Outcome Measures:
  • cumulative patient controlled morphine consumptions [ Time Frame: 24 hours after delivery ] [ Designated as safety issue: No ]
    cumulative patient controlled morphine consumptions 24 hours after delivery


Secondary Outcome Measures:
  • postoperative pain scores [ Time Frame: 1, 4, 6, 12, 24 and 48 hours after delivery ] [ Designated as safety issue: No ]
    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

  • neonatal Apgar scores [ Time Frame: 1 and 5 min aftr delivery ] [ Designated as safety issue: Yes ]
  • Neurologic and adaptive capacity scores [ Time Frame: at 15 min, 2h, 24 and 48 h after delivery ] [ Designated as safety issue: Yes ]
    NACS gives a maximum of 40 with a score >35 denoting vigor.The percentage of infants scoring <35 will be determined.

  • Maternal sedation [ Time Frame: every two hours after delivery, for 48 hours after delivery ] [ Designated as safety issue: Yes ]
    sedation (four-point verbal rating scores (VRS): awake, drowsy, rousable or deep sleep),

  • Maternal nausea and vomiting [ Time Frame: at 24 hours after delivery ] [ Designated as safety issue: Yes ]
    nausea and vomiting (0: no nausea; 1: nausea no vomiting; 2: nausea and vomiting),


Other Outcome Measures:
  • Adverse effects [ Time Frame: 24 hours after delivery ] [ Designated as safety issue: Yes ]
    difficulties in lactation, pruritus, dry mouth, flatulence, hypoglycaemia, dizziness, somnolence, ataxia, vertigo, confusion, incoordination, tremor, dyspnoea, blurred or abnormal vision


Estimated Enrollment: 129
Study Start Date: November 2012
Estimated Study Completion Date: May 2013
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
receive two identical placebo capsules
Drug: Placebo
Ninety minutes before surgery, the parturients receive two identical placebo capsules
Active Comparator: Pregabalin 150 mg group
one capsule of pregabalin 150 mg
Drug: Pregabalin 150 mg group
Ninety minutes before surgery, the parturients receive one capsule of pregabalin 150 mg and one placebo capsule
Active Comparator: Pregabalin 300 mg group
two capsules of pregabalin 150 mg
Drug: Pregabalin 300 mg group
Ninety minutes before surgery, the parturients receive two capsules of pregabalin 150 mg

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 = 43), pregabalin 150 mg (n = 43) and the pregabalin 300 mg (n = 43) 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% (10-12.5 mg) and fentanyl 20 µg. After the umbilical cord is clamped, a 5-10 IU infusion of oxytocin in 500 mL of lactated Ringer's solution will be infused.

A paediatrician blinded to study group allocation will recordApgar 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.6 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 ondansetron 4 mg as required.

  Eligibility

Ages Eligible for Study:   18 Years to 38 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • spinal anesthesia
  • elective cesarean delivery
  • breech presentation
  • cephalopelvic disproportion
  • previous caesarean delivery
  • American Society of Anesthesiologists class I and II

Exclusion Criteria:

  • communication barriers
  • cardiovascular diseases
  • renal diseases
  • hepatic diseases
  • endocrinal diseases
  • neuropsychiatric diseases
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01719705

Contacts
Contact: Samah A El Kenany, MD +201002262557 sk_20022000@yahoo.com

Locations
Egypt
College of Medicine, Mansoura University Not yet recruiting
Mansoura, DK, Egypt, 050
Sub-Investigator: Mohamed R El Tahan, MD         
Mansoura University Hospitals Recruiting
Mansoura, DK, Egypt, 050
Contact: Mohamed R El Tahan, M.D.    +966569371849    mohamedrefaateltahan@yahoo.com   
Sponsors and Collaborators
Mansoura University
Investigators
Principal Investigator: Samah A El Kenany, MD Anethesiology Dept, College of Medicine, Mansoura University
Study Chair: Mohamed R El Tahan, M.D. Mansoura University
  More Information

No publications provided

Responsible Party: Mohamed R El Tahan, Associate Professor of Anesthesiology & SICU, Mansoura University
ClinicalTrials.gov Identifier: NCT01719705     History of Changes
Other Study ID Numbers: R/60
Study First Received: October 28, 2012
Last Updated: November 15, 2012
Health Authority: Egypt: Ministry of Higher Education

Keywords provided by Mansoura University:
caesarean delivery
spinal anesthesia
pregabalin
postoperative pain
morphine

Additional relevant MeSH terms:
Pregabalin
Gamma-Aminobutyric Acid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anticonvulsants
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014