Assessing Ketorolac (Toradol) at Oocyte Retrieval (Alleviate)

August 30, 2023 updated by: Shady Grove Fertility Reproductive Science Center

A Randomized Blinded Placebo Controlled Trial Assessing Ketorolac (Toradol) at Oocyte Retrieval

To determine if a nonsteroidal anti-inflammatory drug (NSAID), Ketorolac (Toradol), can improve pain control and decrease narcotic use after undergoing egg retrieval.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Postoperative pain control is an essential component to any surgical procedure. Surgery represents a time during which opioid-naïve patients may be exposed to narcotics, risking opioid related complications and future opioid-use disorder. Approximately 150,000 oocyte retrievals are performed per year in the United States, according to the 2017 Assisted Reproductive Technology National Summary Report. A reduction in exposure to narcotics in this field has significant public health implications, particularly given that approximately 6% of new persistent opioid use occurs following minor surgical procedures.

Ketorolac (Toradol) has been demonstrated to be a safe and efficacious agent to achieve pain control postoperatively with no significant increase in adverse events.

The purpose of this prospective randomized blinded placebo controlled trial is to determine if a nonsteroidal anti-inflammatory drug (NSAID), Ketorolac (Toradol), can improve pain control and decrease narcotic use after undergoing egg retrieval.

Approximately 400 women (n=200 in each arm) will be enrolled according to the inclusion/exclusion criteria among patients of Shady Grove Fertility. Participants will undergo a standard in vitro fertilization cycle (IVF) followed by egg retrieval (ER). Participants will be randomized to receive either IV ketorolac or IV placebo at the conclusion of the egg retrieval, administered by the anesthesia provider. All enrolled patients will receive standard post-operative pain management. The investigational component of this study lies in assessing post-operative pain control in the immediate post-operative period and in the post-operative period after discharge as reflected by pain scores and narcotic medication usage.

Study Type

Interventional

Enrollment (Estimated)

400

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Maryland
      • Rockville, Maryland, United States, 20850
        • Recruiting
        • Shady Grove Fertility Reproductive Science Center
        • Contact:
        • Principal Investigator:
          • Kathleen Devine, MD
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Shady Grove Fertility Reproductive Science Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Signed informed consent
  2. Females over 18 years of age who are scheduled to undergo oocyte retrieval
  3. Patients must be able to read and understand written English or have an appropriate certified medical translator available.
  4. Standard eligibility criteria to undergo IVF and embryo transfer at Shady Grove

Exclusion Criteria:

  1. Known allergy to ketorolac
  2. Those with known medical conditions precluding them from ketorolac use (active peptic ulcer disease, recent or history of hemorrhage or perforation, known renal or hepatic insufficiency, suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, bleeding disorders, recent myocardial infarction, or stroke.)
  3. BMI ≥ 40 kg/m2
  4. History of substance abuse
  5. Chronic opioid use
  6. Transabdominal oocyte retrieval

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Standard post-operative pain management + Ketorolac (Toradol)
Subject will undergo an IVF cycle with ovarian hyperstimulation and oocyte retrieval. Standard protocols will be used for both study groups and involve administration of gonadotropins to stimulate ovarian follicle growth and regular monitoring with ultrasound and serum estradiol and progesterone levels until follicles reach a desired size. Human Chorionic Gonadotropin (HCG) or leuprolide acetate will be administered to trigger final oocyte maturation prior to oocyte retrieval under anesthesia. On the day of oocyte retrieval, the anesthesia provider will provide syringes of IV ketorolac (30 mg if ≥50 kg or 15 mg if <50 kg per manufacturer dosing) or IV placebo (saline). If assigned to the study arm, IV ketorolac will be administered by the anesthesia provider. All enrolled patients will receive standard post-operative pain management. Patients will be contacted post-operatively, to access pain scores and record the amount of the prescribed narcotic medications utilized since discharge.
Drug: Ketorolac (Toradol)
IV Ketorolac (Toradol) will be administered at conclusion of oocyte retrieval. All enrolled patients will receive standard post-operative pain management.
Placebo Comparator: Standard post-operative pain management + Placebo (saline)
Subject will undergo an IVF cycle with ovarian hyperstimulation and oocyte retrieval. Standard protocols will be used for both study groups and involve administration of gonadotropins to stimulate ovarian follicle growth and regular monitoring with ultrasound and serum estradiol and progesterone levels until follicles reach a desired size. HCG or leuprolide acetate will be administered to trigger final oocyte maturation prior to oocyte retrieval under anesthesia. On the day of oocyte retrieval, the anesthesia provider will provide syringes of IV ketorolac (30 mg if ≥50 kg or 15 mg if <50 kg per manufacturer dosing) or IV placebo (saline). If assigned to the control arm, IV placebo (saline) will be administered by the anesthesia provider. All enrolled patients will receive standard post-operative pain management. Patients will be contacted post-operatively, to access pain scores and record the amount of the prescribed narcotic medications utilized since discharge.
Other: Placebo (saline)
IV Placebo (saline) will be administered at conclusion of oocyte retrieval. All enrolled patients will receive standard post-operative pain management.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Administration of IV narcotic for rescue analgesia during recovery in the post anesthesia care unit (PACU)
Time Frame: Oocyte retrieval procedure day
The primary objective is to evaluate the use of ketorolac as a safe and effective analgesic after transvaginal oocyte retrieval (TVOR) by assessing the number of patients requiring additional analgesia with IV narcotic during recovery in the post anesthesia care unit (PACU).
Oocyte retrieval procedure day

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose of narcotic for rescue analgesia during recovery in the PACU
Time Frame: Oocyte retrieval procedure day
Dose of narcotic administered for rescue analgesia during recovery in the PACU
Oocyte retrieval procedure day
Type of narcotic for rescue analgesia during recovery in the PACU
Time Frame: Oocyte retrieval procedure day
Type of narcotic administered for rescue analgesia during recovery in the PACU
Oocyte retrieval procedure day
Intensity of pain at baseline
Time Frame: Oocyte retrieval procedure day
Pain (measured on a scale of 0 (no pain) to 10 (worst pain imaginable)): baseline pain score
Oocyte retrieval procedure day
Intensity of pain in PACU
Time Frame: Oocyte retrieval procedure day
Pain (measured on a scale of 0 (no pain) to 10 (worst pain imaginable)): PACU pain scores (scored 0-10)
Oocyte retrieval procedure day
Intensity of pain after discharge
Time Frame: From oocyte retrieval procedure day up to 1 week post oocyte retrieval
Pain (measured on a scale of 0 (no pain) to 10 (worst pain imaginable)): Home pain scores (scored 0-10)
From oocyte retrieval procedure day up to 1 week post oocyte retrieval
Home narcotic use
Time Frame: From oocyte retrieval procedure day up to 1 week post oocyte retrieval
Home post-operative narcotic use (recorded as number of pills)
From oocyte retrieval procedure day up to 1 week post oocyte retrieval
Incidence of complications and adverse events
Time Frame: From oocyte retrieval procedure day up to 1 week post oocyte retrieval
Data will be collected on the oocyte retrieval procedure including complications and adverse events in the intra-operative and post-operative periods
From oocyte retrieval procedure day up to 1 week post oocyte retrieval
Biochemical pregnancy rate for patients who proceed to a fresh embryo transfer.
Time Frame: From date of randomization until ~10 days following embryo transfer
Biochemical pregnancy is defined as the detection of beta HCG above 5 IU/L
From date of randomization until ~10 days following embryo transfer
Clinical pregnancy rate for patients who proceed to a fresh embryo transfer.
Time Frame: From date of randomization until 5-8 weeks estimated gestational age
Clinical pregnancy is defined as the presence of a gestational sac(s)
From date of randomization until 5-8 weeks estimated gestational age
Implantation rate for patients who proceed to a fresh embryo transfer.
Time Frame: From date of randomization until 7-8 weeks estimated gestational age
Implantation rate is defined as the maximum number of gestational sacs per patient
From date of randomization until 7-8 weeks estimated gestational age
Ongoing implantation rate for patients who proceed to a fresh embryo transfer.
Time Frame: From date of randomization until 7-8 weeks estimated gestational age
The ongoing implantation rate is defined as maximum number of fetal heartbeats divided by total number of embryos transferred
From date of randomization until 7-8 weeks estimated gestational age
Pregnancy loss rate for patients who proceed to a fresh embryo transfer.
Time Frame: From date of randomization until pregnancy loss, assessed up to 11 months
Miscarriage; either biochemical or clinical pregnancy loss. Biochemical pregnancy loss is defined as initial positive beta HCG that did not progress to clinical pregnancy. Clinical pregnancy loss is defined as clinical pregnancy not progressing to live birth. Total pregnancy loss is defined as biochemical and clinical pregnancy loss (initial positive beta HCG that did not progress to live birth).
From date of randomization until pregnancy loss, assessed up to 11 months
Live birth rate for patients who proceed to a fresh embryo transfer.
Time Frame: From date of randomization until live born infant at an estimated gestational age of at least 23 weeks or greater, assessed up to 11 months
Live birth is defined as birth of a liveborn infant at an estimated gestational age of at least 23 weeks or greater.
From date of randomization until live born infant at an estimated gestational age of at least 23 weeks or greater, assessed up to 11 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shady Grove Fertility Reproductive Science Center

Investigators

  • Principal Investigator: Kathleen Devine, MD, Shady Grove Fertility Reproductive Science Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 10, 2022

Primary Completion (Estimated)

December 1, 2023

Study Completion (Estimated)

January 1, 2025

Study Registration Dates

First Submitted

August 22, 2023

First Submitted That Met QC Criteria

August 30, 2023

First Posted (Actual)

September 7, 2023

Study Record Updates

Last Update Posted (Actual)

September 7, 2023

Last Update Submitted That Met QC Criteria

August 30, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TORA-IVF-01

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe