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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Labor Pain
• Intervention / Treatment: Drug: Tramadol Hydrochloride; Drug: Paracetamol (acetaminophen); Drug: Placebo (Saline Solution)

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.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ricardo A. Gutierrez-Ramirez, MD, MSc; Phone Number: +50497546940; Email: ricardo.gutierrez@unah.edu.hn

Study Locations

• Honduras
  • Francisco Morazán Department
    • Tegucigalpa, Francisco Morazán Department, Honduras, 11101
      • Recruiting
      • Hospital Escuela
      • Contact: Ricardo A. Gutierrez Ramirez, MD, MSc.; Phone Number: 50497546940; Email: ricardo.gutierrez@unah.edu.hn
      • Principal Investigator: Jessica M. Peña Ordoñez, MD
      • Sub-Investigator: Jose A. Mendoza Rodriguez, MD
    • Tegucigalpa, Francisco Morazán Department, Honduras, 11101
      • Recruiting
      • Instituto Hondureño de Seguridad Social
      • Contact: Ricardo A. Gutierrez-Ramirez, MD, MSc.; Phone Number: 50497546940; Email: ricardo.gutierrez@unah.edu.hn
      • Principal Investigator: Ethel A. Cruz Valdivieso, MD
      • Sub-Investigator: Raphael Amador Umanzor, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tramadol Group; Participants receive a single dose of tramadol 100 mg intravenously at the onset of active labor (cervical dilation ≥4 cm with regular contractions).	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.
Experimental: Paracetamol Group; Participants receive a single dose of paracetamol 1 g intravenously (slow infusion) at the onset of active labor (cervical dilation ≥4 cm with regular contractions).	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).
Placebo Comparator: Placebo Group; Participants receive a single dose of 10 mL 0.9% saline solution intravenously at the onset of active labor (cervical dilation ≥4 cm with regular contractions).	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Active Labor	Time in minutes from administration of study intervention (at onset of active labor defined as cervical dilation ≥4 cm with regular contractions) to complete cervical dilation (10 cm) or delivery, whichever occurs first. Measured and recorded by attending obstetric staff using standardized timing protocols.	From intervention administration (at active labor onset) up to 12 hours.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Expulsive Phase (Second Stage)	Time in minutes from complete cervical dilation (10 cm) to fetal expulsion. Measured and recorded by attending obstetric staff.	During delivery, from complete cervical dilation up to 120 minutes.
Type of Delivery	Classification of delivery outcome: spontaneous vaginal delivery, instrumental delivery (forceps or vacuum), or cesarean section. Assessed by attending obstetrician.	At delivery
Need for Oxytocin Augmentation	Requirement for additional oxytocin administration to augment uterine contractions during labor. Recorded as yes/no, including dose and timing if applicable.	During labor (from intervention administration up to 24 hours).
Maternal Adverse Events	Occurrence of any adverse events potentially related to the intervention, including: nausea, vomiting, somnolence, dizziness, headache, pruritus, hypotension (systolic BP <90 mmHg), or allergic reactions. Severity graded as mild, moderate, or severe.	From intervention administration up to 24 hours postpartum.
Neonatal Apgar Score at 5 Minutes	Apgar score assessed at 5 minutes after birth. Score ranges from 0-10, with higher scores indicating better neonatal condition.	At 5 minutes after birth.
Neonatal Complications	Occurrence of neonatal complications including: Apgar score <7 at 5 minutes, meconium-stained amniotic fluid, need for neonatal resuscitation, NICU admission, or neonatal asphyxia	From birth up to 48 hours, through hospital discharge.
Pain Scores (Visual Analog Scale)	Maternal pain assessed using Visual Analog Scale (VAS) from 0 (no pain) to 10 (worst imaginable pain). Measured at baseline (pre-intervention), 30 minutes, 1 hour, and 2 hours post-intervention.	Pre-intervention, and at 30 minutes, 1 hour, and 2 hours post-intervention.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subgroup Analysis by Maternal Age	Comparison of primary and secondary outcomes stratified by maternal age categories (<20 years, 20-35 years, >35 years).	Throughout study period, average of six months

Collaborators and Investigators

• Sponsor: Universidad Nacional Autonoma de Honduras

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Estimated): February 15, 2026
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: February 17, 2026
• First Submitted That Met QC Criteria: February 24, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Acetaminophen; Paracetamol; Tramadol; Labor Pain; Labor Duration
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Labor Pain; Organic Chemicals; Pharmaceutical Preparations; Lipids; Anilides; Amides; Aniline Compounds; Amines; Acetanilides; Crystalloid Solutions; Isotonic Solutions; Solutions; Alcohols; Cyclohexanols; Hexanols; Fatty Alcohols; Dimethylamines; Methylamines; Acetaminophen; Tramadol; Saline Solution
• Other Study ID Numbers: PO-UNAH-49-7-2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Individual participant data (anonymized) will be shared for scientific purposes related to obstetric analgesia and labor management. Only de-identified datasets will be shared with qualified researchers upon reasonable request and with appropriate ethics committee approval. Participants will be informed of data sharing plans during the informed consent process and may opt out.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No