Rct Assessing Pregnancy - Piroxicam for Ec With Levonorgestrel (RAPPEL)

This randomized controlled trial will test oral levonorgestrel + piroxicam vs. levonorgestrel + placebo for emergency contraception in a representative U.S. population that has higher pregnancy risk than in the prior study because of higher weights, different intercourse patterns, and different clinic accessibility. Data from this project will inform clinical practice in the U.S. and beyond for those desiring the most effective method of emergency contraception pills.

Study Overview

• Status: Not yet recruiting
• Conditions: Contraception; Emergency Contraception; COX-2 Inhibitor
• Intervention / Treatment: Drug: Levonorgestrel 1.5 mg and Piroxicam 40 mg; Drug: Oral LNG + Placebo

• Study Type: Interventional
• Enrollment (Estimated): 1458
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: David Turok, MD, MPH; Phone Number: 801-213-2995; Email: david.turok@hsc.utah.edu
• Study Contact Backup: Name: Sarah DeLuca, MPH; Phone Number: 801-213-2995; Email: sarah.deluca@hsc.utah.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Between 16-35 years old and desire LNG for EC
• Unprotected intercourse within 72 hours
• Biologically capable of pregnancy
• Regular menstrual cycle 21-35 days long with known LMP +/- 3 days
• Working cell phone number that receives text messages (for Aim 3 participants phone with capability to download and use the Oova application and submit data)
• Fluent in English and/or Spanish
• Willing to comply with the study requirements including 1-month urine pregnancy test
• No known contraindications to oral LNG or piroxicam - For secondary outcome assessing pregnancy risk for participants receiving study drug on day of ovulation or later - are currently using a menstrual cycle tracking application and can demonstrate according to the application that they are on the day of ovulation or post ovulation.

Exclusion Criteria:

• Current pregnancy (+urine pregnancy test in clinic)

  • Breastfeeding, post abortion or postpartum without resuming menstruation
  • Use of hormonal contraception (including oral EC) within seven days of enrollment
  • Use of NSAIDs (ibuprofen, naproxen, celecoxib, diclofenac, aspirin) in the prior week
  • Highly effective contraception including permanent contraception (including partner with vasectomy), IUD, or contraceptive implant
  • Allergy to LNG or piroxicam
  • Desires UPA for EC

History of stroke, myocardia infarction, ischemic heart disease, uncontrolled hypertension, congestive heart failure, peptic ulcer disease, renal or hepatic failure. Currently taking anticoagulants, corticosteroids, cyclosporine, lithium, methotrexate, or tacrolimus.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral LNG + Piroxicam; Compare EC efficacy among 1,458 U.S. participants randomly assigned 3:1 to oral LNG + piroxicam vs. oral LNG + placebo. This ARM will provide participants Oral LNG plus Piroxicam.	Drug: Levonorgestrel 1.5 mg and Piroxicam 40 mg; The study intervention is a combination of Levonorgestrel 1.5 mg and Piroxicam 40 mg for emergency contraception. Participants will be randomized 3:1 to this vs. Levonorgestrel 1.5 mg and placebo.
Placebo Comparator: Oral LNG + Placebo; Compare EC efficacy among 1,458 U.S. participants randomly assigned 3:1 to oral LNG + piroxicam vs. oral LNG + placebo. This Arm will assign participants to oral lng plus a placebo.	Drug: Oral LNG + Placebo; The study intervention is a combination of Levonorgestrel 1.5 mg and placebo for emergency contraception. Participants will be randomized 3:1 to Levonorgestrel 1.5 mg and Piroxicam vs. this option.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EC efficacy between the two study groups measured by pregnancy status four weeks after EC use.	The study's primary outcome is a confirmed pregnancy at four weeks (+/- 5 days) after EC study drug consumption as determined by a positive high sensitivity urine pregnancy test or clinical documentation of a pregnancy at any time that dates back to a fertilization date that is within 5 days of EC study drug consumption.	One month after consuming study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pregnancy risk for participants weighing ≥75 kg compared between the two drug treatment groups.	The primary outcome for this aim will be the pregnancy risk for participants weighing ≥75 kg compared between the two drug treatment groups. We will compare the pregnancy risk among the subset of participants weighing ≥75 kg randomized to LNG + piroxicam vs. LNG + placebo.	One month after consuming study drug
Test hypothesis that LNG + piroxicam will yield superior proportion of pregnancies prevented among participants using EC on the day of ovulation and post-ovulation compared to LNG + placebo.	Aim 3 statistical analyses will use superiority design to test the hypothesis that LNG + piroxicam will yield superior proportion of pregnancies prevented among participants using EC on the day of ovulation and post-ovulation compared to LNG + placebo.	One month after consuming study drug.

Collaborators and Investigators

• Sponsor: University of Utah
• Investigators: Principal Investigator: David Turok, MD, MPH, University of Utah

Publications and helpful links

General Publications

• Li RHW, Lo SST, Gemzell-Danielsson K, Fong CHY, Ho PC, Ng EHY. Oral emergency contraception with levonorgestrel plus piroxicam: a randomised double-blind placebo-controlled trial. Lancet. 2023 Sep 9;402(10405):851-858. doi: 10.1016/S0140-6736(23)01240-0. Epub 2023 Aug 16.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2027
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): November 1, 2031

Study Registration Dates

• First Submitted: February 26, 2026
• First Submitted That Met QC Criteria: February 26, 2026
• First Posted (Actual): March 4, 2026

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: February 26, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Contraception; Emergency Contraception; Piroxicam
• Additional Relevant MeSH Terms: Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Thiazines; Norpregnenes; Norpregnanes; Norsteroids; Norgestrel; Levonorgestrel; Piroxicam
• Other Study ID Numbers: 00180510

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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