Analgesic Efficacy and Obstetric Effects of Tramadol, Paracetamol and Placebo in Active Labor

Official title

Analgesic Efficacy and Obstetric Effects of Tramadol, Paracetamol and Placebo in Active Labor: A Randomized Double-Blind Controlled Trial

Overview

This randomized, double-blind, placebo-controlled trial aims to compare the analgesic efficacy and obstetric effects of tramadol (100 mg IV) versus paracetamol (1 g IV) versus placebo (saline solution) in nulliparous women during active labor. The primary outcome is duration of active labor (minutes). Secondary outcomes include duration of expulsive phase, type of delivery, need for oxytocin augmentation, maternal adverse events (nausea, vomiting, somnolence, hypotension), and neonatal outcomes (Apgar scores at 1 and 5 minutes, NICU admission). The study hypothesizes that tramadol significantly reduces active labor duration compared to paracetamol and placebo, without compromising maternal or neonatal safety. A total of 300 nulliparous women (100 per group) will be enrolled at Hospital Escuela, Tegucigalpa, Honduras.

Detailed description

This is a randomized, double-blind, parallel-group, superiority efficacy trial comparing three interventions: tramadol 100 mg IV, paracetamol 1 g IV, and placebo (10 mL 0.9% saline solution) administered at the onset of active labor (cervical dilation ≥4 cm with regular contractions). The study design follows CONSORT guidelines for randomized controlled trials. Randomization will be performed using REDCap's automated randomization module in variable block sizes, ensuring allocation concealment. Double-blinding is maintained: participants, care providers, and outcome assessors are masked to group assignment. The primary endpoint is duration of active labor (minutes from intervention administration to complete cervical dilation). Secondary endpoints include: duration of expulsive phase (minutes), type of delivery (spontaneous vaginal, instrumental, cesarean), need for oxytocin augmentation, maternal adverse events (nausea, vomiting, somnolence, hypotension, pruritus, dizziness), neonatal Apgar scores at 1 and 5 minutes, birth weight, meconium-stained amniotic fluid, NICU admission, and neonatal asphyxia. Data collection includes sociodemographic variables (age, education, marital status, occupation), obstetric variables (gestational age, prenatal care visits, BMI, membrane status, cervical dilation at intervention, baseline fetal heart rate), and pain scores (Visual Analog Scale pre-intervention, 30 min, 1h, 2h post-intervention). Statistical analysis includes ANOVA or Kruskal-Wallis for continuous variables, chi-square for categorical variables, and logistic regression for binary outcomes, with significance set at p\<0.05. A Data Safety Monitoring Board will oversee safety every 3 months. The study is funded by Universidad Nacional Autónoma de Honduras and will be conducted at Hospital Escuela, Tegucigalpa, from Feb. 2026 to June 2026.

Interventions

• Drug Tramadol Hydrochloride
  Tramadol 100 mg administered as a single intravenous dose at the onset of active labor. Tramadol is an atypical opioid analgesic with serotonin and noradrenaline reuptake inhibition properties. The dose is within standard clinical ranges for obstetric analgesia. Administration is performed by trained medical personnel following institutional protocols. Participants are monitored for adverse effects including nausea, vomiting, somnolence, dizziness, and hypotension.
• Drug Paracetamol (acetaminophen)
  Paracetamol 1 g administered as a single intravenous slow infusion at the onset of active labor. Paracetamol is a central analgesic acting through COX-3 inhibition in the central nervous system. It is widely used during pregnancy and labor due to its favorable safety profile. Administration is performed by trained medical personnel following institutional protocols. Participants are monitored for adverse effects including nausea, vomiting, and allergic reactions (rare).
• Drug Placebo (Saline Solution)
  Placebo consisting of 10 mL 0.9% saline solution administered as a single intravenous dose at the onset of active labor. The appearance and administration procedure are identical to the active interventions to maintain blinding. No pharmacological active ingredients are present. Administration is performed by trained medical personnel following institutional protocols.

Primary outcome measures

• Duration of Active Labor [Time frame: From intervention administration (at active labor onset) up to 12 hours.]

Secondary outcome measures (7)

• Duration of Expulsive Phase (Second Stage) [Time frame: During delivery, from complete cervical dilation up to 120 minutes.]
• Type of Delivery [Time frame: At delivery]
• Need for Oxytocin Augmentation [Time frame: During labor (from intervention administration up to 24 hours).]
• Maternal Adverse Events [Time frame: From intervention administration up to 24 hours postpartum.]
• Neonatal Apgar Score at 5 Minutes [Time frame: At 5 minutes after birth.]
• Neonatal Complications [Time frame: From birth up to 48 hours, through hospital discharge.]
• Pain Scores (Visual Analog Scale) [Time frame: Pre-intervention, and at 30 minutes, 1 hour, and 2 hours post-intervention.]

Eligibility criteria

Inclusion criteria

• Nulliparous pregnant women
• Age between 15 and 45 years
• Singleton pregnancy, term (37-41 weeks gestation)
• Cephalic presentation
• Active labor defined as cervical dilation ≥4 cm with regular contractions
• Signed informed consent

Exclusion criteria

• Multiple gestation or high-risk pregnancy (preeclampsia, gestational diabetes, etc.)
• Known allergy or contraindication to tramadol or paracetamol
• Recent use (less than 6 hours) of any analgesic medication
• Previous cesarean section or other uterine surgery
• Active infection or fever at admission
• Inability to provide informed consent due to mental or communication conditions
• Non-cephalic presentation
• Rupture of membranes >18 hours without labor
• Participation in another clinical trial within the last 3 months

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Honduras · 2 centers

• Hospital Escuela — Tegucigalpa
• Instituto Hondureño de Seguridad Social — Tegucigalpa

Publications

• Usman M, Ashraf M, Khokhar MI, Ashiq B, Masood MI, Afzal S, Omer O, Ali M, Qadir MI. Comparative pharmacokinetics of levofloxacin in healthy volunteers and in patients suffering from typhoid Fever. Iran J Pharm Res. 2013 Winter;12(1):147-54. PMID 24250583

Identifiers

NCT: NCT07440069 · PO-UNAH-49-7-2026

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗