Assessing Ketorolac (Toradol) at Oocyte Retrieval

Postoperative Pain Clinical Trial

— Alleviate  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06026553
• Other study ID #: TORA-IVF-01
• Status: Recruiting
• Phase: Phase 1
• Start date: August 10, 2022
• Est. completion date: January 2025

Study information

• Verified date: August 2023
• Source: Shady Grove Fertility Reproductive Science Center
• Contact: Tasha Newsome
• Phone: (301)545-1289
• Email: tasha.newsome[@]sgfertility.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: January 2025
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Embryo Transfer
• Infertility
• Infertility, Female
• Oocyte Retrieval
• Pain, Postoperative
• Postoperative Pain

Intervention

Drug:
• Ketorolac (Toradol)
IV Ketorolac (Toradol) will be administered at conclusion of oocyte retrieval. All enrolled patients will receive standard post-operative pain management.

Other:
• Placebo (saline)
IV Placebo (saline) will be administered at conclusion of oocyte retrieval. All enrolled patients will receive standard post-operative pain management.

Locations

Country	Name	City	State
United States	Shady Grove Fertility Reproductive Science Center	Fairfax	Virginia
United States	Shady Grove Fertility Reproductive Science Center	Rockville	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Shady Grove Fertility Reproductive Science Center

Country where clinical trial is conducted

United States, 

References & Publications (14)

Brown CR, Moodie JE, Wild VM, Bynum LJ. Comparison of intravenous ketorolac tromethamine and morphine sulfate in the treatment of postoperative pain. Pharmacotherapy. 1990;10(6 ( Pt 2)):116S-121S. — View Citation

Centers for Disease Control and Prevention. 2017 Assisted Reproductive Technology National Summary Report. US Dept of Health and Human Services; 2021.

Gobble RM, Hoang HLT, Kachniarz B, Orgill DP. Ketorolac does not increase perioperative bleeding: a meta-analysis of randomized controlled trials. Plast Reconstr Surg. 2014 Mar;133(3):741-755. doi: 10.1097/01.prs.0000438459.60474.b5. — View Citation

Greer IA. Effects of ketorolac tromethamine on hemostasis. Pharmacotherapy. 1990;10(6 ( Pt 2)):71S-76S. — View Citation

Kang J, Chapdelaine P, Laberge PY, Fortier MA. Functional characterization of prostaglandin transporter and terminal prostaglandin synthases during decidualization of human endometrial stromal cells. Hum Reprod. 2006 Mar;21(3):592-9. doi: 10.1093/humrep/dei400. Epub 2005 Dec 8. — View Citation

Kato T, Sampei M, Saito K, Morisaki N, Urayama KY. Depressive symptoms, anxiety, and quality of life of Japanese women at initiation of ART treatment. Sci Rep. 2021 Apr 6;11(1):7538. doi: 10.1038/s41598-021-87057-6. Erratum In: Sci Rep. 2021 Nov 17;11(1):22793. — View Citation

Kiani Z, Simbar M, Hajian S, Zayeri F. The prevalence of depression symptoms among infertile women: a systematic review and meta-analysis. Fertil Res Pract. 2021 Mar 4;7(1):6. doi: 10.1186/s40738-021-00098-3. — View Citation

Maslin B, Lipana L, Roth B, Kodumudi G, Vadivelu N. Safety Considerations in the Use of Ketorolac for Postoperative Pain. Curr Drug Saf. 2017;12(1):67-73. doi: 10.2174/1574886311666160719154420. — View Citation

Mesen TB, Kacemi-Bourhim L, Marshburn PB, Usadi RS, Matthews M, Norton HJ, Hurst BS. The effect of ketorolac on pregnancy rates when used immediately after oocyte retrieval. Fertil Steril. 2013 Sep;100(3):725-8. doi: 10.1016/j.fertnstert.2013.04.048. Epub 2013 May 28. — View Citation

Seidler EA, Vaughan DA, Leung AQ, Sakkas D, Ryley DA, Penzias AS. Routine ketorolac at oocyte retrieval decreases postoperative narcotic use by more than 50. F S Rep. 2021 Feb 10;2(2):156-160. doi: 10.1016/j.xfre.2021.02.003. eCollection 2021 Jun. — View Citation

Siristatidis CS, Basios G, Pergialiotis V, Vogiatzi P. Aspirin for in vitro fertilisation. Cochrane Database Syst Rev. 2016 Nov 3;11(11):CD004832. doi: 10.1002/14651858.CD004832.pub4. — View Citation

Waljee JF, Li L, Brummett CM, Englesbe MJ. Iatrogenic Opioid Dependence in the United States: Are Surgeons the Gatekeepers? Ann Surg. 2017 Apr;265(4):728-730. doi: 10.1097/SLA.0000000000001904. No abstract available. — View Citation

Walter JR. Ketorolac use after oocyte retrieval: doing our part to combat the opioid crisis. F S Rep. 2021 Mar 12;2(2):142-143. doi: 10.1016/j.xfre.2021.03.001. eCollection 2021 Jun. No abstract available. — View Citation

Wilson N, Kariisa M, Seth P, Smith H 4th, Davis NL. Drug and Opioid-Involved Overdose Deaths - United States, 2017-2018. MMWR Morb Mortal Wkly Rep. 2020 Mar 20;69(11):290-297. doi: 10.15585/mmwr.mm6911a4. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Administration of IV narcotic for rescue analgesia during recovery in the post anesthesia care unit (PACU)	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	Dose of narcotic for rescue analgesia during recovery in the PACU	Dose of narcotic administered for rescue analgesia during recovery in the PACU	Oocyte retrieval procedure day
Secondary	Type of narcotic for rescue analgesia during recovery in the PACU	Type of narcotic administered for rescue analgesia during recovery in the PACU	Oocyte retrieval procedure day
Secondary	Intensity of pain at baseline	Pain (measured on a scale of 0 (no pain) to 10 (worst pain imaginable)): baseline pain score	Oocyte retrieval procedure day
Secondary	Intensity of pain in PACU	Pain (measured on a scale of 0 (no pain) to 10 (worst pain imaginable)): PACU pain scores (scored 0-10)	Oocyte retrieval procedure day
Secondary	Intensity of pain after discharge	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
Secondary	Home narcotic use	Home post-operative narcotic use (recorded as number of pills)	From oocyte retrieval procedure day up to 1 week post oocyte retrieval
Secondary	Incidence of complications and adverse events	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
Secondary	Biochemical pregnancy rate for patients who proceed to a fresh 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
Secondary	Clinical pregnancy rate for patients who proceed to a fresh embryo transfer.	Clinical pregnancy is defined as the presence of a gestational sac(s)	From date of randomization until 5-8 weeks estimated gestational age
Secondary	Implantation rate for patients who proceed to a fresh embryo transfer.	Implantation rate is defined as the maximum number of gestational sacs per patient	From date of randomization until 7-8 weeks estimated gestational age
Secondary	Ongoing implantation rate for patients who proceed to a fresh embryo transfer.	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
Secondary	Pregnancy loss rate for patients who proceed to a fresh embryo transfer.	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
Secondary	Live birth rate for patients who proceed to a fresh embryo transfer.	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