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Trial registered on ANZCTR


Registration number
ACTRN12612001165875
Ethics application status
Approved
Date submitted
27/10/2012
Date registered
2/11/2012
Date last updated
2/11/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
Maternal and neonatal effects of remifentanil in women undergoing ceasarean section in relation to multidrug resistance protein 1 (MDR1) and mu-opioid receptor (OPRM) polymorphisms
Scientific title
A randomized, double-blind study to evaluate the efficacy and safety of remifentanil in subjects undergoing ceasarean section in relation to multidrug resistance protein 1 (MDR1) and mu-opioid receptor (OPRM) polymorphisms
Secondary ID [1] 281447 0
Nil
Universal Trial Number (UTN)
U1111-1136-4050
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
pregnant women with hypertension, chronic or gestational, including preeclampsia indicated to caesarean section 287709 0
Condition category
Condition code
Anaesthesiology 288045 288045 0 0
Anaesthetics

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will receive an intravenous bolus of remifentanil once 30 s before the introduction into general anaesthesia. The dosage will be calculated according to start body weight of patient. Induction of anaesthesia will be performed with intravenous thiopental 5mg kg-1. Trachea will be intubated after muscle paralysis with intravenous suxamethonium 75-125 mg, with intravenous atracurium 0,35 mg kg-1 administered to achieve further muscle ralaxation. Anaesthesia will be maintained with inhalation of sevoflurane 0,7 vol % in combination with 50 % nitrous oxide in oxygen, until the time of delivery. After birth and umbilical cord ligation intravenous sufentanil 0,3-0,5 mg kg-1, as required, inhalated nitrous oxide in oxygen (50/50 %, v/v) and inhalated sevoflurane (0,7-1 %) will be administered to achieve adequate sedation and analgesia till the end of surgery. Standart monitoring included non-invasive blood pressure measurement, pulse oximetry (SpO2), capnography, inspired oxygen fraction, electrocardiography (heart rate, ST segment trending), inspired and expired gas fraction. The bispectral index (BIS) values will be also monitored and observation values will be noted at 2.5 min intervals during 15 minutes. Time note will be taken of the following events: transfer to operation hall, administration of remifentanil, laryngoscopy and endotracheal intubation, skin incision, uterine incision, delivery, the end of the operation and extubation. Neonates will be assessed by using Apgar scores, possible respiratory depression. Exclusion criterias will be multiparity, gestational age < 35 weeks, estimated fetal weight < 2500g, hypoxia or signs of fetal stress and mother´s hypotension.
Intervention code [1] 285953 0
Treatment: Drugs
Comparator / control treatment
no treatment
Control group
Active

Outcomes
Primary outcome [1] 288257 0
sufficiency of anesthesia - suppression of autonomic reactions by blood pressure measurement (systolic arterial pressure, mean arterial pressure, heart rate)
Timepoint [1] 288257 0
Values will be noted at 2.5 min intervals during 15 minutes from the beginning till the end of the caesarean section. Also time note of the following events: transfer to operation hall, administration of remifentanil, laryngoscopy and endotracheal intubation, skin incision, uterine incision, delivery, the end of the operation and extubation will be noted.
Primary outcome [2] 288280 0
depth of anesthesia - the bispectral index (BIS)
Timepoint [2] 288280 0
Values will be noted at 2.5 min intervals during 15 minutes from the beginning till the end of the caesarean section.
Primary outcome [3] 288281 0
course of anesthesia - pulse oximetry (SpO2), capnography, inspired oxygen fraction, inspired and expired gas fraction.
Timepoint [3] 288281 0
Values will be noted at 2.5 min intervals during 15 minutes from the beginning till the end of the caesarean section.
Secondary outcome [1] 299701 0
neonatal characteristics - Apgar score
Timepoint [1] 299701 0
Neonates will be evaluated by standart Apgar score at 1st, 5th and 10th minute.
Secondary outcome [2] 299753 0
Resuscitative measures of newborn - bag-mask ventilation, tactile stimulation, oxygen tubing
Timepoint [2] 299753 0
Neonates will be monitored 10min after birth for possible respiratory depression.

Eligibility
Key inclusion criteria
cesarean section, hypertension, preeclampsia
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
multiparity, gestational age < 35 weeks, estimated fetal weight < 2500g, hypoxia or signs of fetal stress and mother´s hypotension

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
14/12/2011
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
160
Accrual to date
Final
Recruitment outside Australia
Country [1] 4656 0
Czech Republic
State/province [1] 4656 0
Prague

Funding & Sponsors
Funding source category [1] 286215 0
University
Name [1] 286215 0
Charles University in Prague, 1st faculty of medecine
Country [1] 286215 0
Czech Republic
Primary sponsor type
Government body
Name
Interni grantove agentury Ministerstva zdravotnictvi (IGA)
Address
Ministerstvo zdravotnictvi
Palackeho nam. 4
128 01 Praha 2
Country
Czech Republic
Secondary sponsor category [1] 285024 0
None
Name [1] 285024 0
Address [1] 285024 0
Country [1] 285024 0
Other collaborator category [1] 277140 0
Hospital
Name [1] 277140 0
General University Hospital
Address [1] 277140 0
U Nemocnice 2
128 08 Praha 2
Country [1] 277140 0
Czech Republic

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288290 0
Eticka komise Vseobecne fakultni nemocnice v Praze
Ethics committee address [1] 288290 0
Na Bojisti 1, III.patro
128 08 Praha 2
Ethics committee country [1] 288290 0
Czech Republic
Date submitted for ethics approval [1] 288290 0
Approval date [1] 288290 0
Ethics approval number [1] 288290 0

Summary
Brief summary
Opioids are considered as the gold standard for achieving good anesthetic action. However, opioids are usually avoided at the induction of general anesthesia for caesarean delivery until the delivery of newborn because of the risk of placental transfer and neonatal respiratory depression. The absence of opioids can cause a lack of analgesia. Moreover, insufficient anesthesia is manifested by exaggerated response to painful stimulus with increased catecholamine levels in the blood resulting in increased blood pressure, heart rate, intracranial pressure and decreased uteroplacental blood flow. This effect may be particularly risky in pregnant women with hypertension, chronic or gestational, including preeclampsia for a high risk of cerebrovascular accident. Consequences of hypertension can results even in malignant arythmia, pulmonary edema and hypoxia of the newborn One of the best suited opioid for providing labor analgesia using a systemic approach could be remifentanil. Remifentanil has a small volume of distribution with a rapid redistribution phase , and a short elimination half-life. Remifentanil quickly transfers across the placenta with a mean umbilical vein to maternal artery concentration ratio, but it is metabolized rapidly by nonspecific plasma and tissue esterases in the fetus and thus should not produce neonatal depression. This pharmacokinetic profile gives remifentanil an advantage over other opioids. P-glycoprotein (P-gp), which is highly expressed in the maternal-facing apical membrane of the syncytiotrophoblast, plays an important role in drug transfer across the placental barrier icluding opioids. Genetic polymorphisms are believed to be a major cause of the varaibility of its activity. Of particular interest are three SNPs C3435T in exon 26, and G2677T/A in exon 21 and the linkage between them. Another possible source of interindividual variability in the reaction to opioids including remifentanil are polymorphisms of OPRM1 gene coding mu-opioid receptor. There is great interest in one common polymorphism of OPRM1, p. A118G.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34881 0
Address 34881 0
Country 34881 0
Phone 34881 0
Fax 34881 0
Email 34881 0
Contact person for public queries
Name 18128 0
Hana Bakhouche
Address 18128 0
Farmakologicky ustav 1. LF UK
Albertov 4
12800 Praha 2
Country 18128 0
Czech Republic
Phone 18128 0
+420 224968113
Fax 18128 0
+420 224967015
Email 18128 0
[email protected]
Contact person for scientific queries
Name 9056 0
Hana Bakhouche
Address 9056 0
Farmakologicky ustav 1. LF UK
Albertov 4
12800 Praha 2
Country 9056 0
Czech Republic
Phone 9056 0
+420 224968113
Fax 9056 0
+420 224967015
Email 9056 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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