Prospective Effect of Intravenous Ketorolac on Opioid Use, EBL and Complications Following Cesarean Delivery

NCT02509312 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: Ketorolac-1
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

In this randomized, double-blind control trial to evaluate the effect of ketorolac given at the time of cord clamp has on estimated blood loss and postcesarean pain control. Patients will be randomized to either placebo or ketorolac prior to surgery. Those randomized to ketorolac will receive ketorolac at cord clamp and three additional doses every 6 hours (total 4 doses/24 hours). Those in the placebo group will receive normal saline during those time periods. Our primary outcome is to assess whether intra-operative ketorolac increases the estimated blood loss during Cesarean delivery.

Conditions

Analgesia, Obstetrical; Postpartum Hemorrhage; Opioid Use; Nonsteroidals (NSAIDs)Toxicity; Coagulation Defect; Postpartum; Postoperative Pain; Ketorolac Adverse Reaction; Blood Loss, Postoperative

Keywords

Analgesia, Obstetrical; Blood Loss, Surgical; Analgesics, Opioid/administration & dosage; Cyclooxygenase Inhibitors/administration & dosage; Cesarean Delivery; Female; Humans; Ketorolac/administration & dosage; Hydromorphone/administration & dosage; Pain, Postoperative/drug therapy; Pregnancy; Morphine/administration & dosage; Cesarean Section Complications; Ketorolac

Outcome Measures

Primary Outcomes (1)

• Estimated Blood Loss (EBL)

  Estimation of blood loss during surgery

  Immediately post-op

Secondary Outcomes (11)

• Post-Partum Hemorrhage

  0 - 24 hours post-partum

• Corrected Change in Hct on POD1.

  POD1

• Uterotonic Doses

  0 - 24 hours post-partum

• Units of Packed Reb Blood Cell Transfused

  Intra-op until 24 hours post-partum.

• Hydromorphone Use

  0 - 24 hours post-partum

Study Arms (2)

Experimental

EXPERIMENTAL

Patients in this arm will be given ketorolac at cord clamp with standard dose of 30 mg, then 3 additional 30 mg doses every 6 hours

Drug: Ketorolac

Control

PLACEBO COMPARATOR

Patients in this arm will be given a placebo medication at cord clamp, and then 3 additional doses of placebo every 6 hours.

Drug: Placebo

Interventions

Ketorolac DRUG

Patients in the experimental arm will receive ketorolac 30 mg in 1 ml at the time of cord clamp and then for 3 more doses every 6 hours.

Also known as: Toradol

Experimental

Placebo DRUG

Patients in the control arm will receive normal saline 1 ml at the time of cord clamp and then for 3 more doses every 6 hours.

Control

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Patients undergoing a scheduled or non-scheduled, non-urgent primary or repeat Cesarean delivery between 37-42 weeks gestational age,
• Viable singleton intra-uterine pregnancy,
• Patients undergoing a scheduled or unscheduled, non-emergent/non-urgent Cesarean delivery for placenta previa or vasa previa,
• Neuraxial anesthesia with combined spinal-epidural placed for surgery,
• Patients must be 18 years or older as well as willing and able to provide informed consent.

You may not qualify if:

• Patients unable or unwilling to provide informed consent,
• Urgent or emergent Cesarean delivery
• Multiple fetal gestations (\>1 intrauterine pregnancy),
• Cesarean delivery for bleeding such as placental abruption or actively bleeding placenta previa or vasa previa,
• Contraindication to NSAID use eg: allergy, chronic renal disease,
• Patients with acute or chronic platelet dysfunction (e.g.: idiopathic thrombocytopenic purpura, HELLP syndrome),
• Platelets \<100k,
• History of peptic ulcer disease,
• Inherited or acquired coagulopathies or bleeding disorder, (disseminated intravascular coagulopathy, hemophilia),
• Suspected or proven placenta accreta, increta or percreta,
• Inability to receive epidural morphine,
• Diagnosed chronic pain disorder on chronic adjunct or opioid analgesia,
• Use of general anesthesia during procedure.
• \- EBL \> 1000 ml prior to cord clamp

Sponsors & Collaborators

• University Hospitals Cleveland Medical Center: lead

Study Sites (1)

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Related Publications (7)

• Blackburn A, Stevens JD, Wheatley RG, Madej TH, Hunter D. Balanced analgesia with intravenous ketorolac and patient-controlled morphine following lower abdominal surgery. J Clin Anesth. 1995 Mar;7(2):103-8. doi: 10.1016/0952-8180(94)00040-b.

  PMID: 7598916 BACKGROUND

• Diemunsch P, Alt M, Diemunsch AM, Treisser A. Post cesarean analgesia with ketorolac tromethamine and uterine atonia. Eur J Obstet Gynecol Reprod Biol. 1997 Apr;72(2):205-6. doi: 10.1016/s0301-2115(96)02682-6. No abstract available.

  PMID: 9134403 BACKGROUND

• Pavy TJ, Paech MJ, Evans SF. The effect of intravenous ketorolac on opioid requirement and pain after cesarean delivery. Anesth Analg. 2001 Apr;92(4):1010-4. doi: 10.1097/00000539-200104000-00038.

  PMID: 11273941 BACKGROUND

• Lowder JL, Shackelford DP, Holbert D, Beste TM. A randomized, controlled trial to compare ketorolac tromethamine versus placebo after cesarean section to reduce pain and narcotic usage. Am J Obstet Gynecol. 2003 Dec;189(6):1559-62; discussion 1562. doi: 10.1016/j.ajog.2003.08.014.

  PMID: 14710063 BACKGROUND

• El-Tahan MR, Warda OM, Yasseen AM, Attallah MM, Matter MK. A randomized study of the effects of preoperative ketorolac on general anaesthesia for caesarean section. Int J Obstet Anesth. 2007 Jul;16(3):214-20. doi: 10.1016/j.ijoa.2007.01.012. Epub 2007 Apr 24.

  PMID: 17459695 BACKGROUND

• Elhakim M, Fathy A, Amine H, Saeed A, Mekawy M. Effect of i.v. tenoxicam during caesarean delivery on platelet activity. Acta Anaesthesiol Scand. 2000 May;44(5):555-9. doi: 10.1034/j.1399-6576.2000.00512.x.

  PMID: 10786742 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

MeSH Terms

Conditions

Agnosia; Postpartum Hemorrhage; Hemostatic Disorders; Pain, Postoperative; Postoperative Hemorrhage; Blood Loss, Surgical; Pain

Interventions

Ketorolac; Ketorolac Tromethamine

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Pathologic Processes; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Postoperative Complications; Intraoperative Complications

Intervention Hierarchy (Ancestors)

Indomethacin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Limitations include: * single-center study. * secondary outcomes may not fully represent opioid-sparing and pain seen in a center practicing current SOAP ERAC protocol as patients received epidural and not intrathecal morphine and not all patients received all doses of acetaminophen. * secondary outcomes may not fully represent the opioid-sparing and pain effects of ketorolac, as not all ketorolac patients received all doses of ketorolac.

Results Point of Contact

• Title: John J. Kowalczyk, MD
• Organization: Beth Israel Deaconess Medical Center

jkowalcz@bidmc.harvard.edu

617-667-3112

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo (normal saline) or ketorolac in syringe prepared by the investigational pharmacy with study kit number and blinding key maintained by investigational pharmacy until time of unblinding.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Instructor of Anaesthesia - Beth Israel Deaconess Medical Center, Harvard Medical School / Harvard Medical School

Study Record Dates

• First Submitted: June 11, 2015
• First Posted: July 28, 2015
• Study Start: May 1, 2016
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2017
• Last Updated: June 7, 2022
• Results First Posted: June 7, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)