Alleviate: Assessing Ketorolac (Toradol) at Oocyte Retrieval

Sponsor

Shady Grove Fertility Reproductive Science Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT06026553

Collaborator

(none)

400

Enrollment

Locations

Arms

28.7

Anticipated Duration (Months)

200

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Infertility Infertility, Female Oocyte Retrieval Postoperative Pain Embryo Transfer	Drug: Ketorolac (Toradol) Other: Placebo (saline)	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

400 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Outcomes Assessor)

Masking Description:

Allocation group will not be disclosed to the patient or the physician or the nurse or the outcome assessor. The anesthesia provider administering the IV Ketorolac or Placebo will be unblinded.

Primary Purpose:

Supportive Care

Official Title:

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

Actual Study Start Date :

Aug 10, 2022

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Jan 1, 2025

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Administration of IV narcotic for rescue analgesia during recovery in the post anesthesia care unit (PACU) [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).

Secondary Outcome Measures

Dose of narcotic for rescue analgesia during recovery in the PACU [Oocyte retrieval procedure day]
Dose of narcotic administered for rescue analgesia during recovery in the PACU
Type of narcotic for rescue analgesia during recovery in the PACU [Oocyte retrieval procedure day]
Type of narcotic administered for rescue analgesia during recovery in the PACU
Intensity of pain at baseline [Oocyte retrieval procedure day]
Pain (measured on a scale of 0 (no pain) to 10 (worst pain imaginable)): baseline pain score
Intensity of pain in PACU [Oocyte retrieval procedure day]
Pain (measured on a scale of 0 (no pain) to 10 (worst pain imaginable)): PACU pain scores (scored 0-10)
Intensity of pain after discharge [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)
Home narcotic use [From oocyte retrieval procedure day up to 1 week post oocyte retrieval]
Home post-operative narcotic use (recorded as number of pills)
Incidence of complications and adverse events [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
Biochemical pregnancy rate for patients who proceed to a fresh embryo transfer. [From date of randomization until ~10 days following embryo transfer]
Biochemical pregnancy is defined as the detection of beta HCG above 5 IU/L
Clinical pregnancy rate for patients who proceed to a fresh embryo transfer. [From date of randomization until 5-8 weeks estimated gestational age]
Clinical pregnancy is defined as the presence of a gestational sac(s)
Implantation rate for patients who proceed to a fresh embryo transfer. [From date of randomization until 7-8 weeks estimated gestational age]
Implantation rate is defined as the maximum number of gestational sacs per patient
Ongoing implantation rate for patients who proceed to a fresh embryo transfer. [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
Pregnancy loss rate for patients who proceed to a fresh embryo transfer. [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).
Live birth rate for patients who proceed to a fresh embryo transfer. [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

Known allergy to ketorolac
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.)
BMI ≥ 40 kg/m2
History of substance abuse
Chronic opioid use
Transabdominal oocyte retrieval

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Shady Grove Fertility Reproductive Science Center	Rockville	Maryland	United States	20850
2	Shady Grove Fertility Reproductive Science Center	Fairfax	Virginia	United States	22031