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Trial registered on ANZCTR


Registration number
ACTRN12609000153213
Ethics application status
Approved
Date submitted
29/01/2009
Date registered
18/03/2009
Date last updated
18/03/2009
Type of registration
Retrospectively registered

Titles & IDs
Public title
Meperidine versus valethamate bromide in shortening the duration of labor
Scientific title
Randomized prospective, double blind, placebo-controlled study to compare the efficacy and safety of meperidine and valethamate bromide with placebo for acceleration of labor.
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Shortening the duration of labor 4243 0
Condition category
Condition code
Reproductive Health and Childbirth 4465 4465 0 0
Childbirth and postnatal care
Reproductive Health and Childbirth 4675 4675 0 0
Fertility including in vitro fertilisation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A total of 160 nulliparous term pregnant women undergoing labor induction were randomly assigned to one of three treatment groups using computer generated random number table: 50 mg meperidine in group 1 (n=53) and 16 mg valethamate bromide in group 2 (n=53) as the treatment groups. All medications were given just once time by slow intravenous infusion in about 2 minutes when cervical dilation was about 4-6 cm and the fetal head was well applying. Patient and the doctor who followed the stages of labor were blind to the medication.
Intervention code [1] 3967 0
Treatment: Drugs
Comparator / control treatment
Group 3 served as control group and consisted of 53 women who were given normal saline (0.9 % NaCl) as placebo. The medication was given just once time by slow intravenous infusion in about 2 minutes using injectors containing 10 mL solution (normal saline plus related group’s drug) when fetal head was well applying and uterine contractions were well-established, and cervical dilatation was between 4 and 6 cm. Patient and the doctor who followed the stages of labor were blind to the medication.
Control group
Placebo

Outcomes
Primary outcome [1] 5347 0
Mean injection-delivery interval, monitored by the author who was blind to the medication.
Timepoint [1] 5347 0
from the time of beginning of the intervention to the time of the expulsion of the fetus.
Secondary outcome [1] 8984 0
maternal adverse effects, monitored by the author who was blind to the medication.
Timepoint [1] 8984 0
Monitored constantly throughout the birth after the allocated treatment has been injected into the participant.
Secondary outcome [2] 8985 0
fetal adverse effects, monitored by the author who was blind to the medication.
Timepoint [2] 8985 0
Immediately after delivery .

Eligibility
Key inclusion criteria
otherwise healthy nulliparous women undergoing labor induction between 18 and 30 years old with a term singleton pregnancy, vertex presentation
Minimum age
18 Years
Maximum age
30 Years
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
spontaneous labor, estimated fetal weight > 4000 g, suspicion of cephalopelvic disproportion (CPD), evidence of fetal distress, meperidine or valethamate bromide allergy, previous uterine surgery, active vaginal bleeding, placenta praevia, and use of any kind of analgesia prior randomization.

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)
Group allocation was predetermined and placed in consecutively numbered opaque, sealed envelopes. The next consecutive envelope was drawn after the patient consented to randomization.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization was performed with use of a computer generated random number table.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

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] 1550 0
Turkey
State/province [1] 1550 0

Funding & Sponsors
Funding source category [1] 4425 0
Self funded/Unfunded
Name [1] 4425 0
Dr Bulent Yilmaz
Address [1] 4425 0
Taskent Sokak, 26/8, 06600, Kurtulus, Ankara
Country [1] 4425 0
Turkey
Primary sponsor type
Individual
Name
Dr Sefa Kelekci
Address
Bassehir sokak, 14/8, 06150, Cebeci, Ankara
Country
Turkey
Secondary sponsor category [1] 4228 0
Individual
Name [1] 4228 0
Cavit Kart
Address [1] 4228 0
Camlitepe mah., 2. Dedeefendi sokak, no: 76/9, 06600, Ankara
Country [1] 4228 0
Turkey

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6474 0
Human Research and Ethics Committee of the Zekai Tahir Burak Women's Health Education and Research Hospital
Ethics committee address [1] 6474 0
Ethics committee country [1] 6474 0
Turkey
Date submitted for ethics approval [1] 6474 0
Approval date [1] 6474 0
Ethics approval number [1] 6474 0

Summary
Brief summary
Painless and short labor without causing any adverse effects on the mother and fetus is desired by every pregnant women and a constant aim of active management for obstetricians. The progress of labor is assessed by progressive dilatation of cervix and progressive descent of the presenting part. Protraction of the first stage of labor, one of the components of prolonged labor, is multifactorial, and cervical dilatation is one of the important factors which determines the duration of the first stage of labor and is the end result of all driving forces of uterine contraction against passive tissue resistance.
Failure of progressive dilatation of cervix in labor can cause prolonged labor. In addition to mechanical methods such as cervical membrane sweeping, cervical stretching, and amniotomy, there are various pharmacological methods to facilitate cervical dilatation. The role of oxytocin has been established worldwide in the inducing and augmentation of labor, and prostaglandins have been used in various formulations for induction of labor. Cervical application of hyaluronidase, estradiol and relaxin has also been used with some success. Various drugs such as phloroglucinol, tranquilizers, especially diazepam, opioids, especially meperidine, and antispasmodics such as valethamate bromide, drotaverine hydrochloride and hyosin-N-butyl bromide have been used for shortening the duration of labor.
Meperidine has been widely used for relief of labor pain and dystocia during the first stage of labor since its introduction in the late 1940s. Whereas analgesia is maximal about 30 to 45 minutes after an intramuscular (IM) injection, it develops almost immediately following intravenous administration. Meperidine readily crosses the placenta, and the half life is approximately 13 hours or longer in the newborn. Its depressant effect in the fetus follows closely behind the peak maternal analgesic effect. In the first randomized controlled trial to evaluate the use of meperidine as a way to shorten the duration of labor, meperidine was found the absent of any benefit on labor duration and presence of maternal adverse effects as well as other deleterious effects in the newborn.
Valethamate bromide is both a central and a peripheral antimuscarinic agent, which is a competitive inhibitor of acetylcholine at the muscarinic receptors. After IM administration, onset of action occurs in about 20–30 minutes. Plasma half-life is 4 hours. It crosses the placenta and is secreted in the breast milk. It is completely metabolized in the liver and is excreted in the urine as both unchanged drug and metabolites. Neurotropic and musculotropic actions of valethamate bromide result in relaxation of cervical musculature leading to quick dilatation of the cervix and shortened labor.
The objective of this study was to compare the efficacy, safety and side effects of meperidine, valethamate bromide and placebo in shortening the duration of labor.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29225 0
Address 29225 0
Country 29225 0
Phone 29225 0
Fax 29225 0
Email 29225 0
Contact person for public queries
Name 12472 0
Bulent Yilmaz, MD
Address 12472 0
Taskent Sokak, 26/8, 06600, Kurtulus, Ankara
Country 12472 0
Turkey
Phone 12472 0
+9005053574351
Fax 12472 0
Email 12472 0
drbulentyilmaz@yahoo.com
Contact person for scientific queries
Name 3400 0
Bulent Yilmaz, MD
Address 3400 0
Taskent Sokak, 26/8, 06600, Kurtulus, Ankara
Country 3400 0
Turkey
Phone 3400 0
+9005053574351
Fax 3400 0
Email 3400 0
drbulentyilmaz@yahoo.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