Clinical trial NCT02885350
Conditions: Labor Pain
Sponsor: Helsinki University Central Hospital
Start date: 2016-09-01; Completion date: 2018-05-01
Enrollment: 80 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
In this study the analgesic effect of two different opioids (fentanyl and sufentanil) will be compared when given either intrathecally or epidurally in primiparous parturients during early phase of the labour.

Detailed description:

Arms: arm 1: 20 micrograms of intrathecally administered fentanyl in single dose. Total volume of intrathecal injection 2 ml. arm 2: 100 micrograms of epidurally administered fentanyl in a single dose. Total volume of epidural injection 7 ml. arm 3: 5 micrograms of intrathecally administered sufentanil in a single dose. Total volume of intrathecal injection 2 ml. arm 4: 20 micrograms of epidurally administered sufentanil in a single dose. Total volume of epidural injection 7 ml.
Interventions: intervention 1: Spinal analgesia for labour pain intervention 2: Epidural analgesia for labour pain
Intervention descriptions: intervention 1: Intrathecal dose of either fentanyl or sufentanil delivered by combined spinal-epidural technique intervention 2: Epidural dose of either fentanyl or sufentanil delivered through an epidural catheter.

Protocol documents:
Prot_SAP_001.pdf: 
Spinal or epidural fentanyl or sufentanil for labour pain in the early phase of the labour 
Study identifier: NCT02885350 
 
EudraCT: 2016-000486-23 
Protocol date: 1st Feb 2016 
Ethical review board opinion date: 21st Apr 2016 
Researchers: 
Antti J Väänänen, MD PhD 
 
antti.vaananen@hus.fi 
Matti Kuukasjärvi, MD 
 
matti.kuukasjarvi@hus.fi 
Aydin Tekay, MD, PhD (for CTG recordings) aydin.tekay@hus.fi 
Jouni Ahonen, MD, PhD 
 
Jouni.ahonen@hus.fi 
 
Ethical board:  
University of Helsinki, Research ethics committees 
P.O. BOX 705 (Biomedicum Helsinki 2C) 
FI-00029 HUS, Finland 
 
Research site: 
Helsinki University Central Hospital (Katiloopiston sairaala) 
Sofianlehdonkatu, FI-00610 Helsinki, Finland 
 
 
 


Study plan version #1/01st Feb 2016 
Spinal or epidural fentanyl or sufentanil for labour pain in the early phase of the labour 
Abbreviated name: “Early phase labour analgesia by spinal or epidural analgesic”. 
 
Background 
 
Approximately one third of the parturients experience unbearable pain during labour 
(1). Epidural or spinal opioids and local anesthetics given epidurally or spinally are one of the most 
effective methods to alleviate labour pain. This type of analgesia is widely used in our hospital; in 
2015 at HUS/Katiloopisto hospital 6066 (88 %) of the 7471 parturients received either spinal or 
epidural analgesia for labour. 
 
Neuraxial analgesia carries some side-effects although severe side-effects are very 
rare (2). One of the most common side effects is post-dural puncture headache (PDPH) caused by 
perforation of the membrane separating the spinal and epidural spaces. This risk is estimated to be 
approximately 1.7 % with the pencil point needles used in our hospital (3). With spinal drug 
administration this membrane is always perforated. 
 
With epidural drug administration this intentional perforation of the dural membrane 
and its associated headache syndrome could be avoided. In addition spinal analgesia can be 
administered only at a rather low (lumbal) level of the spine in order to avoid spinal cord injury. In 
some parturients obesity or strong lordosis of the lumbal spine can result in technical difficulties in 
the safe placement of the spinal analgesia and it may be easier to use epidural analgesia. 
 
Administration of intrathecal lipophilic opioid alone (fentanyl or sufentanil) has been 
shown to result in sufficient analgesia in the early phase of the labour without causing motor block 
of the lower limbs or drop of blood pressure due to blockade of the symphatetic neural system (4,5). 
This method is used routinely in our hospital with a spinal fentanyl dose of 25 micrograms. Until May 
2013 our hospital routinely used sufentanil at a dose of 5 micrograms. Alternative option for the 
spinal opioid would be normal epidural analgesia where the local anesthetic dose is ropivacain 20 
mg and fentanyl 100 micrograms. The fentanyl dose of 100 micrograms could be replaced by 
sufentanil at a dose of 20 micrograms (6). 
Purpose of the study 
 
In this prospective randomized study the efficacy of spinal or epidural opioid (fentanyl 
or sufentanil) to alleviate the pain during contraction is studied. The opioid is given as a single 
treatment without any local anesthetics. The primary outcome for the study is the level of analgesia 
achieved in 20 minutes after the administration of the analgesia. The secondary outcomes are the 
rate of on-set of the analgesia measured by visual analog scale bar (VAS 0-100 mm; 100 mm worst 
possible pain; 0 mm no pain) from above 80 mm value (peak during contraction) to under 30 mm 
value and the duration of the analgesia provided by the neuraxial opioid alone. 
Methods 
Parturients 
 
A total of 80 primiparous parturients will be recruited (20 parturients in each of the 
four treatment arms). According to the power calculation we expect to detect a potential difference 


of 15 mm in the VAS scores at standard deviation of 15 mm with an 80 % certainty. Potential 
differences of less than 15 mm are not considered clinically relevant.  
The parturients are ensured not to have any contraindications for spinal/epidural 
analgesia and they have not received any opioid analgesics by any route within 120 minutes prior to 
analgesia administration. The randomization is performed when the parturient asks for regional pain 
relief (i.e. spinal fentanyl according to the institutional practice). The delivery must be in the early 
phase marked by cervical dilatation of 5 cm or less at the time of the investigational analgesia and 
the pain VAS during contraction on the 0-100 mm VAS scale shall be at 80 mm or more. The BMI of 
the parturient at the date of delivery must be 20-35, the pregnancy singleton and the parturient may 
not have allergy for fentanyl, sufentanil or lidocaine. Furthermore, the parturient’s ability to read 
and speak Finnish must be adequate so that she can understand the study and she can be 
interviewed according to the protocol after the analgesia. 
 
The parturient will be given the study brochure prior to painful contractions reach the 
randomization level (VAS 80 mm). If the parturient agrees to participate in the study and fulfills the 
inclusion criteria, she will be randomized in to one of the four treatment arms. 
Interventions 
 
According to the randomization (20 parturients per group) the parturient is 
randomized to receive either fentanyl 20 micrograms intrathecally, fentanyl 100 micrograms 
epidurally, sufentanil 5 micrograms intrathecally or sufentanil 20 micrograms epidurally. The 
intrathecal medications are diluted according to the institutional protocol into the total volume of 2 
ml and epidural medication is diluted into 5 ml volume by sterile saline. 
 
Epidural analgesia is given through the epidural catheter and in all cases epidural 
catheter is flushed with 2 ml of saline at the end of procedure. The neuraxial analgesia procedure is 
performed according to the institutional protocol using Portex combined spinal epidural (CSE) set 
but for epidural drug administration the spinal needle is not used. In both intrathecal (spinal) and 
epidural medication groups, an epidural G18 catheter is left in the lumbal epidural space. 
Blinding 
 
For safety reasons the study will be blinded in such a manner that the parturient or 
the data collector do not know which analgesia is administered. The anesthesiologist providing the 
analgesia will prepare the sterile table and draw the medications outside the delivery room. The 
anesthesia chart will show the randomization code of the parturient. The key to the randomization 
codes is always available in the anesthesia office. Otherwise, the anesthesia report will be filled in a 
normal manner and the subsequent epidural analgesia boluses will be marked normally in the chart. 
The parturient is informed about the procedure using standardized phrases, which do not reveal the 
(spinal or epidural) nature of the analgesia provided for the midwife or the parturient. In both 
treatment groups an identical Portex epidural catheter remains in the back of the parturient. 
 
Data will be collected after the drug delivery by another anesthesiologist who is 
blinded regarding the analgesia provided. 
Follow up and data acquisition 
 
The on-set of analgesia is monitored during each contraction on a 0-100 mm VAS 
scale for up to 30 minutes after the analgesia. The maximum achievable analgesia is expected to be 
achieved within 30 minutes. The fetal heartrate and the parturient’s blood pressure is monitored for 


30 minutes according to institutional protocol for neuraxial analgesia. Pruritus is the most common 
side-effect of the neuraxial opioids and it will be monitored by interview at 0, 10, 20 and 30 minutes. 
The used measurement scale is: 0 = no pruritus; 1 = mild pruritus; 2 = moderate pruritus; 3 =severe 
pruritus; 4 = unbearable pruritus. Potential nausea and vomiting will be documented at 0, 10, 20 and 
30 minutes (for the past 10 minute interval). Also potential changes in the fetal heart rate, potential 
ob/gyn consultations and actions due to these consultations will be recorded. 
Rescue analgesia and subsequent labour analgesia 
 
The parturient can receive additional analgesia through the epidural catheter at the 
earliest 30 minutes after the spinal or epidural opioid administration. At 30-45 minutes after the 
intervention the parturient may get 20 mg ropivacain in 20 ml saline, whereas after 45 minutes a 
dose of 20 mg of ropivacain and 50 micrograms of fentanyl in 20 ml can be given. 
Data to be collected in the trial 
 
Background information (height, weight, duration of pregnancy)  
from primary health care maternity chart 
 
Gestational data (duration of pregnancy) 
 
 
from the hospital Obstetrics software 
 
Prior analgesia during delivery 
 
 
 from the hospital Obstetrics software 
Pain VAS (0-100 mm) immediately prior to investigational analgesia and for each 
contraction thereafter for 30 minutes 
 
Interviewed from the parturient 
Pruritus and nausea at 0; 10; 20; 30 minutes after the analgesia 
 
Interviewed from the parturient 
Timing of the next epidural analgesic dose, cervical dilatation prior to the next 
epidural dose. Information on the analgesia provided by the epidural dose. 
 
 
from the hospital Obstetrics software 
Time of delivery, mode of delivery (cesarean delivery, vacuum assisted delivery), 
potential postpartum operations in the operating theatre. 
 
 
from the hospital Obstetrics software 
 
Fetal heart rate (FHR) 
 
 
automatically registered into the hospital Milou system 
 
Archival of the collected data, processing of personal information regarding parturients 
 
The collected data will be archived at the Department of Anaesthesiology in a locked 
cabinet to which only the investigators have access. When the information is transferred into the 
electronic data file all directly identifying information will be removed (name and date of birth). The 


study participants can be subsequently identified by matching case number with the signed consent 
form. No directly identifying information is saved in the electronic form. 
Analysis of the collected data 
 
For statistical analysis the information is transferred into SPSS software, which is used 
for comparison of the continuous data (background information, pain VAS scores) and categorical 
data (adverse events such as nausea, pruritus). 
The primary outcome is measured in millimeters on a 100 millimeter line and 
processed as a continuous variable with 0 mm indicating no detectable pain and 100 mm indicating 
the worst possible pain. Similarly secondary outcome marker, the duration of analgesia, will be 
recorded in minutes and processed as a continuous variable. The incidence of adverse events will be 
recorded as presence or absence of certain adverse events (pruritus, nausea) and analyzed as a 
categorical variable. 
Chi-squared test will be used for categorical variables while Kruskal-Wallis test for 
independent samples is used for comparisons of continuous variables between the treatment arms.  
The fetal heartrate (CTG) recordings will be retroactively analyzed by an obstetrician 
for potential pathology prior to analgesia and for 30 minutes thereafter. The obstetrician is blinded 
regarding the intervention. 
All data and events are analyzed according to original allocation into respective 
intervention groups. 
 
Completion of the study 
 
Recruiting of the parturients will begin once the required permits have been received. 
The parturients will be recruited during 2016 and the results of the study will be published in a peer 
reviewed journal thereafter. The study will be completed at Helsinki University Central Hospital 
/Katilopisto delivery hospital without external sponsors or funding as part of normal quality 
improvement work. 
 
Ethical considerations 
 
The parturients will be recruited for the study at the very early phase of the labour. 
The institutional normal protocol is to give 25 micrograms of fentanyl intrathecally. The fentanyl 
dose used in this study (20 micrograms) does not differ in terms of efficacy from the 25 microgram 
dose and the efficacy of the other interventions is expected to be in the similar range. Epidural 
delivery of fentanyl or sufentanil alone without local anesthetic has not been previously studied in 
the early phase of the labour. 
 
This study will provide information regarding possible replacement of spinal opioid 
administration with epidural opioid thus avoiding risks and limitations associated with spinal opioid 
delivery. 
 
No placebo control is used in this study and the parturients will not be exposed to 
additional injections or painful maneuvers. It is possible that epidural analgesia does not have as fast 
on-set as spinal analgesia. The only viable option for spinal drug administration currently would be 


epidural analgesia which is not routinely preferred at such early phase of the delivery. Therefore, the 
participating parturients are expected to receive at least as good labour analgesia as those 
parturients who do not participate in the trial. 
References 
1. Hardy JD; Javert CT. Studies on pain: measurements of pain intensity in childbirth. J Clin 
Invest 1949; 28: 153-162. 
2. Jenkins JG. Some immediate serious complications of obstetric analgesia and anaesthesia: a 
prospective study of 145.550 epidurals. Int J Obstet Anesth 2005; 14: 37-42. 
3.  Choi PT; Galinski SE; Takeuchi L; Lucas S; Tamayo C; Jadad AR. PDPH is a common 
complication of neuraxial blockade in parturients: a meta-analysis of obstetrical studies. Can 
J Anaesth 2003; 50: 460-469. 
4. Herman NL; Choi KC; Affleck PJ; Calicott R; Brackin R; Singhai A; Adreasen A; Gadalia F; Fong 
J; Gomillion MC; Hartman JK; Koff HD; Lee SH, Van Decar TK. Analgesia, pruritus, and 
ventilation exhibit a dose-response relationship in parturients receiving intrathecal fentanyl 
during labour. Anesth Analg 1999; 89: 378-383. 
5. Herman NL; Calicott R; Van Decar TK; Conlin G; Tilton J. Determination of the dose-response 
relationship for intrathecal sufentanil in laboring patients. Anesth Analg 1997; 84: 1256-
1261. 
6. Connelly NR; Parker RK; Vallurupalli V; Bhopatkar S; Dunn S. Comparison of epidural fentanyl 
versus epidural sufentanil for analgesia in ambulatory patients in early labor. Anesth Analg. 
2000; 91: 374-378.