Assessing Ketorolac (Toradol) at Oocyte Retrieval

NCT06026553 | Unknown Phase 1 FDA Drug

• 1 other identifier: TORA-IVF-01
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Keywords

Infertility, Female; In Vitro Fertilization; IVF; Oocyte Retrieval; Postoperative Pain Control; NSAID; Ketorolac; Non-Narcotic Analgesia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• Dose of narcotic for rescue analgesia during recovery in the PACU

  Oocyte retrieval procedure day

• Type of narcotic for rescue analgesia during recovery in the PACU

  Oocyte retrieval procedure day

• Intensity of pain at baseline

  Oocyte retrieval procedure day

• Intensity of pain in PACU

  Oocyte retrieval procedure day

• Intensity of pain after discharge

  From oocyte retrieval procedure day up to 1 week post oocyte retrieval

Study Arms (2)

Standard post-operative pain management + Ketorolac (Toradol)

EXPERIMENTAL

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)

Standard post-operative pain management + Placebo (saline)

PLACEBO COMPARATOR

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)

Interventions

Ketorolac (Toradol) DRUG

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

Standard post-operative pain management + Ketorolac (Toradol)

Placebo (saline) OTHER

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

Standard post-operative pain management + Placebo (saline)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: Only female subjects will be recruited for this study as an oocyte retrieval requires ovary(ies) to be present and therefore this is only possible in the biological female sex.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shady Grove Fertility Reproductive Science Center: lead

Study Sites (2)

Shady Grove Fertility Reproductive Science Center

Rockville, Maryland, 20850, United States

RECRUITING

Shady Grove Fertility Reproductive Science Center

Fairfax, Virginia, 22031, United States

RECRUITING

Related Publications (14)

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  PMID: 27429023 BACKGROUND

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

  BACKGROUND

• 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.

  PMID: 32191688 BACKGROUND

• 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.

  PMID: 33663615 BACKGROUND

• 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.

  PMID: 33824373 BACKGROUND

• 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.

  PMID: 34278342 BACKGROUND

• 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.

  PMID: 2082307 BACKGROUND

• 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.

  PMID: 24572864 BACKGROUND

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

  PMID: 2082316 BACKGROUND

• 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.

  PMID: 27440142 BACKGROUND

• 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.

  PMID: 16339169 BACKGROUND

• 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.

  PMID: 23721715 BACKGROUND

• 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.

  PMID: 34278347 BACKGROUND

• 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.

  PMID: 27807847 BACKGROUND

MeSH Terms

Conditions

Infertility; Infertility, Female; Pain, Postoperative

Interventions

Ketorolac; Ketorolac Tromethamine; Sodium Chloride

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Indomethacin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Kathleen Devine, MD

  Shady Grove Fertility Reproductive Science Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tasha Newsome

CONTACT

(301)545-1289; tasha.newsome@sgfertility.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2023
• First Posted: September 7, 2023
• Study Start: August 10, 2022
• Primary Completion: December 1, 2023
• Study Completion: January 1, 2025
• Last Updated: September 7, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)