The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12615001034527
Ethics application status
Approved
Date submitted
21/05/2015
Date registered
6/10/2015
Date last updated
6/10/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
Effects of fentanyl added to intrathecal levobupivacaine on requirement for ephedrine and the newborn in elective cesarean section as a randomized trial.
Scientific title
Effect of fentanyl added to intrathecal levobupivacaine on requirement for ephedrine and the newborn in elective cesarean section
Secondary ID [1] 286744 0
nil
Universal Trial Number (UTN)
nil
Trial acronym
nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
cesarean section 295105 0
Condition category
Condition code
Anaesthesiology 295530 295530 0 0
Anaesthetics
Anaesthesiology 295859 295859 0 0
Other anaesthesiology
Reproductive Health and Childbirth 295860 295860 0 0
Childbirth and postnatal care

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
10 minute before cesarean section intrathecal levobupivacaine 0.5 % (Group I), levobupivacaine 0.5 % + 10 microgram fentanyl (Group II) and levobupivacaine 0.5 % + 25 microgram fentanyl (Group III). Following the induction of spinal anesthesia, the subjects were promptly placed in the supine position and were injected with 5 mg bolus ephedrine, followed by 10 microgram kg-1 min-1 ephedrine infusion.
Infusion was discontinued if Systolic blood pressure value reached >100% of the baseline value,
- Infusion was maintained at 10 microgram kg-1 min-1 if SBP value was between 80% and 100% of the baseline value,
- Infusion was maintained at 20 microgram kg-1 min-1 if SBP value was <80% of the baseline value,
- In addition to 5 mg bonus administration, infusion was maintained at 20 microgram kg-1 min-1 if Systolic blood pressure value was < 90 mmHg.
Intervention code [1] 291896 0
Treatment: Drugs
Comparator / control treatment
Levobupivacaine 0.5 % dose for spinal anesthesia was determined in reference to patient height. Consistent with the values , the subjects were administered with levobupivacaine 0.5 % (Group I) as a control group, levobupivacaine 0.5 % + 10 microgram fentanyl (Group II) and levobupivacaine 0.5 % + 25 microgram fentanyl (Group III). Levobupivacaine volume was decreased to compensate for the fentanyl volume in Group II and Group III.
Control group
Active

Outcomes
Primary outcome [1] 295123 0
Total ephedrine dose administered as assessed using patient medical charts.
Timepoint [1] 295123 0
At the conclusion of the operation, bolus, infused and total ephedrine doses were calculated.
Secondary outcome [1] 314816 0
APGAR scores
Timepoint [1] 314816 0
1 and 5 minutes after birth

Eligibility
Key inclusion criteria
elective cesarean section
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Patients with pre-eclampsia, eclampsia, gestational hypertension, diabetes mellitus, cardiac problems or bleeding diathesis were excluded.

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)
sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table from a statistic book
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Phase 3 / Phase 4
Type of endpoint(s)
Safety
Statistical methods / analysis
One Way Anova and Independent Sample T test were used for intergroup comparisons. Chi square and Fisher’s exact chi square tests were used to evaluate the nonnumerical data. The results were expressed as mean +/- standard deviation and statistical significance was set at p<0.05.
There was also a significantly decreased risk of hypotension with increasing ephedrine dose in a cohort study (X^2 = 9.67; P = 0.002). The final power achieved in detecting a linear dose-response relationship for hypotension varied among studies: 6%, 9%, 27%, 88%, and 99%. There was no association between dose and risk of fetal acidosis in a cohort study (X^2 = 3.06; P = 0.08). There was homogeneity of slopes (X^2 =1.32; P = 0.52). We were calculated with a 95% confidence, an alpha of 0.06 and 95% power the sample size was calculated as 150 cases and 150 controls.
X^2 = 9.67; P = 0.002)
(X^2 = 3.06; P = 0.08)
(X^2 = 1.32; P = 0.52
260 cases and 260 controls were evaluated for this study: Group I (n=266), Group II (n=274) and Group III (n=260)

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 6891 0
Turkey
State/province [1] 6891 0

Funding & Sponsors
Funding source category [1] 291316 0
Government body
Name [1] 291316 0
Republic of Turkey Ministry of Health,
Address [1] 291316 0
Republic of Turkey Ministry of Health,Mithatpasa Cad. No: 3 06434 Sihhiye/Ankara
Country [1] 291316 0
Turkey
Primary sponsor type
Hospital
Name
ATATURK TRAINING AND RESEARCH HOSPITAL
Address
ATATURK TRAINING AND RESEARCH HOSPITAL, 06800, BILKENT ANKARA
Country
Turkey
Secondary sponsor category [1] 289996 0
University
Name [1] 289996 0
YILDIRIM BEYAZIT UNIVERSITY
Address [1] 289996 0
Yildirim Beyazit University, cankiri Caddesi cicek Sokak No:3, Ulus, Altindag,06512 Ankara, Turkey
Country [1] 289996 0
Turkey

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292879 0
ZEKAI TAHIR BURAK HASTANESI ETIK KURULU
Ethics committee address [1] 292879 0
Zekai Tahir Burak Hospital, Hacettepe Mh., Talatpasa Bulvari, 06230 Ankara, Turkey
Ethics committee country [1] 292879 0
Turkey
Date submitted for ethics approval [1] 292879 0
15/09/2012
Approval date [1] 292879 0
15/08/2013
Ethics approval number [1] 292879 0
23145

Summary
Brief summary
Aim: To compare the effects of different doses of fentanyl added to intrathecal levobupivacaine on ephedrine requirement and to evaluate its impact on the fetus in subjects undergoing elective cesarean section.
Methods: A total of 800 parturients scheduled for elective cesarean section were enrolled in the study. Those fulfilling the enrollment criteria were randomly assigned to three groups as Group I (n=266), Group II (n=274) and Group III (n=260). All patients were administered with an infusion of Ringer’s lactate solution at 10-12 mL kg-1 in the preoperative period before spinal anesthesia and at 8-10 mL kg h-1 intraoperatively. The dose of levobupivacaine 0.5% was adjusted in reference to patient heights for spinal anesthesia. While Group I was administered with levobupivacaine 0.5%, Group II was administered with levobupivacaine 0.5% + 10 microgram fentanyl and Group III was administered with levobupivacaine 0.5% + 25 microgram fentanyl. In Group II and Group III, levobupivacaine volume was decreased to compensate for the fentanyl volume. Ephedrine infusion was initiated with 5 mg bolus following the puncture for spinal anesthesia. It was then administered at 10 microgram kg-1 min-1. Ephedrine infusion was maintained with respect to baseline systolic blood pressure throughout the operation; and systolic blood pressure, heart rate, nausea-vomiting score as well as the ephedrine doses administered were recorded.
Results: Total preoperative ephedrine requirement of the groups were established to be 26.07 +/- 16.39 mg in Group I, 20.72 +/- 12.95 mg in Group II and 16.80 +/- 9.40 mg in Group III. Total ephedrine used was observed to be significantly lower in Group III than in it was in Group I (p<0.05). Group I was also established with a lower mean fetal umbilical venous pH value than that observed in Group III (p<0.05).
Conclusion: We conclude that the addition of 25 microgram fentanyl to levobupivacaine, when compared with the administration of levobupivacaine alone, decreases the ephedrine requirement and produces better maternal and newborn hemodynamic stability in elective cesarean section cases administered with spinal anesthesia.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 57382 0
Dr Ayca Ozcan
Address 57382 0
Ataturk Training and Research Hospital, Department of Anaesthesiology,Eskisehir Yolu Uzeri, 06800,Ankara, Turkey
Country 57382 0
Turkey
Phone 57382 0
+905057154125
Fax 57382 0
Email 57382 0
draycaozcan@gmail.com
Contact person for public queries
Name 57383 0
Dr Ayca Ozcan
Address 57383 0
Ataturk Training and Research Hospital, Department of Anaesthesiology,Eskisehir Yolu Uzeri, 06800,Ankara, Turkey
Country 57383 0
Turkey
Phone 57383 0
+905057154125
Fax 57383 0
Email 57383 0
draycaozcan@gmail.com
Contact person for scientific queries
Name 57384 0
Dr Ayca Ozcan
Address 57384 0
Ataturk Training and Research Hospital, Eskisehir Yolu Uzeri, 06800,Ankara, Turkey
Country 57384 0
Turkey
Phone 57384 0
+905057154125
Fax 57384 0
Email 57384 0
draycaozcan@gmail.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary