Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000525280
Ethics application status
Approved
Date submitted
15/01/2018
Date registered
10/04/2018
Date last updated
6/08/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Photoplethysmographic evaluation of sympathectomy during epidural analgesia for vaginal delivery: ropivacaine versus levobupivacaine
Scientific title
Photoplethysmographic evaluation of sympathectomy during epidural analgesia for vaginal delivery in healthy parturients: 0.125% ropivacaine versus 0.125% levobupivacaine
Secondary ID [1] 293770 0
None
Universal Trial Number (UTN)
U1111-1207-6898
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
vaginal delivery 306165 0
lumbar epidural analgesia 306166 0
sympathectomy mediated vasodilation 306167 0
Condition category
Condition code
Anaesthesiology 305277 305277 0 0
Anaesthetics
Reproductive Health and Childbirth 305278 305278 0 0
Childbirth and postnatal care
Cardiovascular 305702 305702 0 0
Normal development and function of the cardiovascular system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Before administration of epidural analgesia, all of the patients will be given a prehydration consisting of 1000 ml Ringer's lactate solution intravenously.
Before administration of epidural analgesia, a non-invasive finger photoplethysmography probe will be placed around the first toe of the left leg, as well as the 3 ECG electrodes which will be placed on the chest and a cuff of the mercury sphygmomanometer which will be placed around the left upper arm.
Every measurement of the finger photoplethysmography signal (measured simultaneously with the ECG) will be recorded between the contractions during labour, in a sequence of 30 seconds and will be automatically storaged in the BIOPAC SS4LA software. The mentioned finger photoplethysmography software enables re-run of every single measurement to extract certain parameters (area under the curve, amplitude and the pulse transit time) from the finger photoplethysmography curve.
Epidural space will be identified in the L3-4 interspace by the loss of resistance technique, using 17 G Tuohy needle, in the lying or left lateral position of the patient. After identification of epidural space, epidural cathether will be inserted 4-5 cm into the epidural space. After the aspiration test and administration of a test dose (3 ml of 2% lidocaine), the patients will be given a bolus dose of epidural analgesia, in the lying position with slightly (up to 30 degrees) elevated head of the bed. The patients will be randomised by the type of the local anesthetic solution given into the epidural space: group 1 will be given 10 ml of 0.125% ropivacaine + 100 mcg of fentanyl and group 2 will be given 10 ml of 0.125% levobupivacaine + 100 mcg of fentanyl. Dose, volume and concentrations of two local anesthetics are the same in both groups, as well as the dose of the opioid added in the mixture. The bolus dose of epidural will be applied in the following manner: first 5 ml of the local anesthetic/opiod solution will be given as a bolus, and the rest of the solution (5 ml) will be given after 3-4 minutes, also as a bolus. The described procedure is a standarised protocol for painless vaginal delivery used at our institution.
The study will be conducted in the labour ward, with a controlled ambient temperature of 24 degrees celsius.
Intervention code [1] 300025 0
Treatment: Drugs
Intervention code [2] 300332 0
Treatment: Devices
Comparator / control treatment
Control treatment is active. Group 2 (patients receiving 10 ml of 0.125% levobupivacaine + 100 mcg of fentanyl) is considered to be the comparator group. Both groups of patients receive the standard of care, i.e. the two types of local anesthetic solution used (0.125% ropivacaine and 0.125% levobupivacaine) are considered to be equally effective (and have equal rates of complications) in providing epidural analgesia for vaginal delivery.
Control group
Active

Outcomes
Primary outcome [1] 304436 0
Difference in the area under the curve of the finger photoplethysmography between the two groups. Area under the curve represents the whole surface area under the finger photoplethysmography curve and is derived from every single finger photoplethysmography measurement. The unit of measurement for the area under the curve of the finger photoplethysmography is mcvs (microvoltseconds).
Timepoint [1] 304436 0
The inital signal (baseline measurement) of the finger photoplethysmography will be recorded together with the ECG signal, before the administration of epidural analgesia. After administration of the whole bolus dose of epidural analgesia, the finger photoplethysmography signal will be measured three more times: 5 minutes, 10 minutes and 20 minutes after administration of the whole bolus dose of epidural analgesia. Conclusively, the finger photoplethysmography signal will be recorded in the four time points:
1. before administration of epidural analgesia
2. 5 minutes after administration of epidural analgesia
3. 10 minutes after administration of epidural analgesia
4. 20 minutes after administration of epidural analgesia
Primary endpoint is considered to be 20 minutes after administration of epidural analgesia.
Secondary outcome [1] 341924 0
Difference between the amplitude of the finger photoplethysmography between the two groups. The amplitude of the finger photoplethysmography represents the maximum height of the finger photoplethysmography curve and is derived form every single finger photoplethysmography measurement. The unit of measurement for the amplitude of the finger photoplethysmography is mcv (microvolts).
Timepoint [1] 341924 0
Before administration of epidural analgesia (baseline measurement), 5, 10 and 20 minutes after administration of epidural analgesia.
Secondary outcome [2] 341925 0
Difference in the pulse transit time between the two groups. The pulse transit time is defined as the the time (in seconds) between the middle of the R wave of the electrocardiogram and the amplitude (maximum height) of the following finger photoplethysmography curve (i.e. the time needed for the pulse to travel from the heart to the peripheral blood vessels).
Timepoint [2] 341925 0
Before administration of epidural analgesia (baseline measurement), 5, 10 and 20 minutes after administration of epidural analgesia.
Secondary outcome [3] 341926 0
Difference in systolic and diastolic blood pressure between the two groups. The systolic and diastolic blood pressure will be measured by the non-invasive mercury sphygmomanometer cuff which will be placed on the left forearm.
Timepoint [3] 341926 0
Before administration of epidural analgesia (baseline measurement), 5, 10 and 20 minutes after administration of epidural analgesia.
Secondary outcome [4] 341927 0
Difference in visual analogue scale of pain (VAS score) between the two groups.
Timepoint [4] 341927 0
Before administration of epidural analgesia (baseline measurement), 5, 10 and 20 minutes after administration of epidural analgesia.
Secondary outcome [5] 344249 0
Any episode of the maternal hypotension will be recorded in both of the groups by the manual non-invasive mercury sphygmomanometer. Maternal hypotension is defined as a drop of systolic blood pressure below the 90 mmHg.
Timepoint [5] 344249 0
Any time during the time interval of data collection (up to 20 minutes after administration of epidural analgesia).
Secondary outcome [6] 344250 0
Any abnormality of the fetal heart rate (decelerations) will be recorded in both of the groups by the cardiotocography which is continuously recorded during vaginal delivery in all of the patients.
Timepoint [6] 344250 0
Any time during the time interval of data collection (up to 20 minutes after administration of epidural analgesia).

Eligibility
Key inclusion criteria
The study will include all of the patients in whom lumbar epidural analgesia, as a standard method for painless vaginal delivery, is indicated.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Any kind of hypertensive disorder.
Vasoactive drug therapy.
Obesity (BMI>30)
Peripheral blood vessel disease (deep venous thrombosis, Raynaud's syndrome)
Failed epidural analgesia.
Uncooperation (movement of the legs during recording of the finger photoplethysmography signal)

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)
Allocation was concealed by the sealed envelopes which were marked, either as group 1 (ropivacaine), or group 2 (levobupivacaine).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation which was done by using the coin-tossing procedure.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
The same participants (healthy women giving birth) receiving the same treatment (epidural analgesia), with equivalent concentrations of different drugs (0.125% ropivacaine or 0.125% levobupivacaine).
Phase
Not Applicable
Type of endpoint/s
Pharmacodynamics
Statistical methods / analysis
Sample size was measured by using the sample size test in a programme MedCalc 9.5.1.0. (MedCalc Software, Mariakerke, Belgium), on the basis of a pilot study which included 5 participants per group. Mean values of the area under the curve of the finger photoplethysmography signal, measured 20 minutes after administration of epidural analgesia, were calculated for both groups together with standard deviations: 0,08699 +/- 0,05150 for group 1 (ropivacaine) and 0,1502 +/- 0,1030 for group 2 (levobupivacaine). On the basis of the difference of means between the two groups (0,06321) and standard deviations, a sample size of 28 patients per group was calculated. Type I error (alpha, significance), was set as 0.05 and type II error (beta, power) was set as 0.20. Ratio of sample size of group1/group, was set as 1.
Continous demographic variables (age, body weight, body height and body mass index) will be compared between the two groups by using Mann-Whitney test or t-test for independent samples.
Categorical demographic variables (parity) will be compared between the two groups by using the Chi-square test.
Blood pressure, VAS score and all the parameters derived from the finger photoplethysmography signal (area under the curve, amplitude and pulse transit time) will be compared between the two groups (in every single time point) by using the RM-ANOVA test. The statistical program which will be used is MedCalc 9.5.1.0 (MedCalc Software, Mariakerke, Belgium). P values will be set as lower than 0.05.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
15/04/2018
Date of last participant enrolment
Anticipated
Actual
2/08/2018
Date of last data collection
Anticipated
Actual
2/08/2018
Sample size
Target
56
Accrual to date
Final
60
Recruitment outside Australia
Country [1] 9488 0
Croatia
State/province [1] 9488 0

Funding & Sponsors
Funding source category [1] 298386 0
Hospital
Name [1] 298386 0
Clinic for Obstetrics and Gynecology; University Clinical Hospital Center Zagreb
Country [1] 298386 0
Croatia
Primary sponsor type
Hospital
Name
Clinic for Obstetrics and Gynecology; University Clinical Hospital Center Zagreb
Address
Petrova 13, 10000 Zagreb; Croatia
Country
Croatia
Secondary sponsor category [1] 297515 0
None
Name [1] 297515 0
Address [1] 297515 0
Country [1] 297515 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299379 0
Ethical Committee of the University Clinical Hospital Center Zagreb
Ethics committee address [1] 299379 0
Kišpaticeva 12, 10000 Zagreb; Croatia
Ethics committee country [1] 299379 0
Croatia
Date submitted for ethics approval [1] 299379 0
01/05/2017
Approval date [1] 299379 0
16/05/2017
Ethics approval number [1] 299379 0
02/21 AG
Ethics committee name [2] 299380 0
Ethical Committee of the Clinic for Obstetrics and Gynecology
Ethics committee address [2] 299380 0
Petrova 13, 10000 Zagreb; Croatia
Ethics committee country [2] 299380 0
Croatia
Date submitted for ethics approval [2] 299380 0
01/03/2017
Approval date [2] 299380 0
09/03/2017
Ethics approval number [2] 299380 0
021-1/38-17

Summary
Brief summary
It is possible to evaluate the activity of sympathetic nervous system during central neuraxial blocks by analyzing the curve of the finger photoplethysmography. By using finger photoplethysmography as a surrogate method for evaluation of sympathetic nervous system activity, it is possible to compare and quantify the potential difference in the degree of sympathectomy between 0.125% levobupivacaine and 0.125% ropivacaine during epidural analgesia for vaginal delivery. Finger photoplethysmography is also a potential method for early detection of complications that occur as a consequence of sympathectomy (maternal hypotension, fetal bradicardia and eventually emergent cesarean section) When taking into consideration that ropivacine has a lower potential of cardiovascular toxicity compared to levobupivacaine, we hypothesised that ropivacaine, during epidural analgesia for vaginal delivery, also causes a lower level of sympathectomy than levobupivacaine,
Trial website
Trial related presentations / publications
Public notes
The trial was registered after the actual date of the first patient enrollment. Due to the mentioned fact (and the underlying ehtical issue), all of the authors agreed to temporary suspend the ongoing trial and restart patient enrollment after the trial is retrospectively registered at the ANZCTR. After the trial was registered (10.04.2018.), we continued recruiting the patients (we excluded from the study the patients that were included before the registration).

Contacts
Principal investigator
Name 80230 0
Dr Krešimir Reiner
Address 80230 0
Clinic for Obstetrics and Gynecology, University Clinical Hospital Center Zagreb;
Petrova 13, 10000 Zagreb; Croatia
Country 80230 0
Croatia
Phone 80230 0
+385 91 761 5364
Fax 80230 0
Email 80230 0
[email protected]
Contact person for public queries
Name 80231 0
Dr Krešimir Reiner
Address 80231 0
Clinic for Obstetrics and Gynecology, University Clinical Hospital Center Zagreb;
Petrova 13, 10000 Zagreb; Croatia
Country 80231 0
Croatia
Phone 80231 0
+385 917615364
Fax 80231 0
Email 80231 0
[email protected]
Contact person for scientific queries
Name 80232 0
Dr Krešimir Reiner
Address 80232 0
Clinic for Obstetrics and Gynecology, University Clinical Hospital Center Zagreb;
Petrova 13, 10000 Zagreb; Croatia
Country 80232 0
Croatia
Phone 80232 0
+385 917615364
Fax 80232 0
Email 80232 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

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbasePhotoplethysmographic evaluation of sympathectomy during lumbar epidural analgesia: A randomized comparison of 0.125% ropivacaine and 0.125% levobupivacaine.2019https://dx.doi.org/10.1111/aas.13351
N.B. These documents automatically identified may not have been verified by the study sponsor.