Intravenous Ketamine for Pain Control During First Trimester Surgical Abortion

NCT03751423 | Suspended Phase 3 DMC

• 1 other identifier: OBGY-KET-18
• Study Type: interventional
• Target: 123
• Locations: 1 country
• Sites: 1

Brief Summary

A therapeutic abortion is one of the most common procedures performed in Canada, with approximately 100,000 occurring annually. 95% of induced abortions are done surgically, with just over two thirds of these procedures taking place in the first trimester. This study will be a randomized, controlled, double-blinded, single-centre superiority trial with three parallel groups; oral morphine vs intravenous fentanyl vs intravenous ketamine. The primary outcome will be immediate post-operative pain following a first trimester therapeutic abortion as assessed using the visual analogue scale. Randomization will be performed as block randomization with a 1:1:1 allocation ratio. In total, 123 participants will be recruited and randomized, with 41 being assigned to each treatment arm. This study will be conducted at the Women's Clinic at Kingston General Hospital in Kingston, Ontario, Canada. Women from Kingston and the surrounding areas are referred to this clinic and can self-refer for therapeutic abortion. The investogators hope that this research will move us towards a better form of pain control for our participants undergoing first trimester surgical abortion, without increasing length of stay, side effects, or adverse events. This, in turn, will hopefully improve access to optimal pain control to participants undergoing first trimester surgical abortion in an outpatient setting.

Conditions

Abortion in First Trimester

Keywords

procedural sedation; ketamine; fentanyl; morphine

Outcome Measures

Primary Outcomes (1)

• VAS Pain Score - Immediate Post-Procedure

  The primary outcome measure is mean difference in immediate post-operative pain measured by the visual analogue pain scale (VAS). The VAS is a validated tool for research in operative pain management. Using this scale, participants rate their current pain on a scale from 0 to 10 by drawing an "x" on the horizontal line. This line is 10cm long and the participant's pain level is measured using a ruler to the millimeter mark and translated to a score out of 100mm. If the "x" falls between millimeter marks on the ruler the reader will round up to the nearest mark.

  Immediate Post-Procedure

Secondary Outcomes (9)

• VAS Pain Score - Prior to Discharge

  Prior to discharge from recovery room on day of procedure (typically within 1h post-procedure)

• Length of Stay in Recovery

  Day of Procedure

• Satisfaction with Pain Control - Prior to Discharge

  Prior to discharge from recovery room on day of procedure (typically within 1h post-procedure)

• Medication Side Effects

  Prior to discharge from recovery room on day of procedure (typically within 1h post-procedure)

• Provider Assessment of Intra-Operative Pain Management

  Intra-Operative

Study Arms (3)

PO Morphine & IV Placebo

ACTIVE COMPARATOR

One third of study participants will be randomized to this local standard of care arm.

Drug: PO Morphine; Drug: IV Placebo

IV Fentanyl & PO Placebo

ACTIVE COMPARATOR

One third of study participants will be randomized to this current gold standard of care arm.

Drug: IV Fentanyl; Drug: PO Placebo

IV Ketamine & PO Placebo

EXPERIMENTAL

One third of study participants will be randomized to this experimental arm.

Drug: IV Ketamine; Drug: PO Placebo

Interventions

PO Morphine DRUG

10-20mg oral morphine depending on such factors as weight (100-200mcg/kg), previous opiate exposure (opiate naïve vs opiate sensitized), and participant's previous experiences with opiate medications for painful procedures. Dosing will be determined at the discretion of the surgical provider in clinic that day, as per standard of care.

Also known as: Morphine Sulphate

PO Morphine & IV Placebo

IV Fentanyl DRUG

0.5-1mcg/kg IV fentanyl over 2 minutes repeated every 5 minutes as needed until appropriate analgesia is reached.

Also known as: Fentanyl Citrate Injection

IV Fentanyl & PO Placebo

IV Ketamine DRUG

200-500mcg/kg IV over 2 minutes repeated every 5 minutes as needed until appropriate analgesia is reached

Also known as: Ketamine Hydrochloride Injection

IV Ketamine & PO Placebo

PO Placebo DRUG

A standard placebo pill, the same size, shape and colour of the oral morphine. The placebo will be administered to the participants randomized to the IV ketamine and IV fentanyl during pre-op in the same manner the oral morphine would be administered.

Also known as: Oral Placebo Pill

IV Fentanyl & PO Placebo; IV Ketamine & PO Placebo

IV Placebo DRUG

This normal saline will be administered to the participants randomized to the oral morphine group during the procedure in the same manner that IV fentanyl or IV ketamine would be administered.

Also known as: Normal Saline

PO Morphine & IV Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed first trimester pregnancy with an ultrasound showing a viable intrauterine pregnancy with a gestational age of less than 12 weeks since the last menstrual period
• Unwanted pregnancy and consented to undergo a first trimester surgical abortion

You may not qualify if:

• Age \<18 years at the time of study enrollment
• Known allergy or sensitivity to any of the medications used in the study
• Any serious medical comorbidity that would make IV sedation contraindicated in an outpatient setting (ex. Heart disease, lung disease)

Sponsors & Collaborators

• Dr. Marie Eve Sophie Bussiere-Cote: lead

Study Sites (1)

Queen's University

Kingston, Ontario, K7L2V7, Canada

Location

Related Publications (22)

• Induced abortions reported in Canada in 2016. Ottawa: Canadian Institute for Health Information; 2018. Available at: https://www.cihi.ca/en/induced-abortions-reported-in-canada-in-2016. Accessed on July 29, 2018.

  BACKGROUND

• Costescu D, Guilbert E. No. 360-Induced Abortion: Surgical Abortion and Second Trimester Medical Methods. J Obstet Gynaecol Can. 2018 Jun;40(6):750-783. doi: 10.1016/j.jogc.2017.12.010.

  PMID: 29861084 BACKGROUND

• Allen RH, Fitzmaurice G, Lifford KL, Lasic M, Goldberg AB. Oral compared with intravenous sedation for first-trimester surgical abortion: a randomized controlled trial. Obstet Gynecol. 2009 Feb;113(2 Pt 1):276-83. doi: 10.1097/AOG.0b013e3181938758.

  PMID: 19155895 BACKGROUND

• Agostini A, Maruani J, Roblin P, Champion J, Cravello L, Gamerre M. A double-blind, randomized controlled trial of the use of a 50:50 mixture of nitrous oxide/oxygen in legal abortions. Contraception. 2012 Jul;86(1):79-83. doi: 10.1016/j.contraception.2011.11.015. Epub 2012 Jan 20.

  PMID: 22264664 BACKGROUND

• Kan AS, Caves N, Wong SY, Ng EH, Ho PC. A double-blind, randomized controlled trial on the use of a 50:50 mixture of nitrous oxide/oxygen in pain relief during suction evacuation for the first trimester pregnancy termination. Hum Reprod. 2006 Oct;21(10):2606-11. doi: 10.1093/humrep/del234. Epub 2006 Jun 21.

  PMID: 16790607 BACKGROUND

• Strayer RJ, Nelson LS. Adverse events associated with ketamine for procedural sedation in adults. Am J Emerg Med. 2008 Nov;26(9):985-1028. doi: 10.1016/j.ajem.2007.12.005.

  PMID: 19091264 BACKGROUND

• Galloon S. Ketamine for dilatation and curettage. Can Anaesth Soc J. 1971 Nov;18(6):600-13. doi: 10.1007/BF03026180. No abstract available.

  PMID: 5119802 BACKGROUND

• Hejja P, Galloon S. A consideration of ketamine dreams. Can Anaesth Soc J. 1975 Jan;22(1):100-5. doi: 10.1007/BF03004825.

  PMID: 1109698 BACKGROUND

• Erbguth PH, Reiman B, Klein RL. The influence of chlorpromazine, diazepam, and droperidol on emergence from ketamine. Anesth Analg. 1972 Sep-Oct;51(5):693-700. No abstract available.

  PMID: 4560720 BACKGROUND

• Hervey WH, Hustead RF. Ketamine for dilatation and currettage procedures: patient acceptance. Anesth Analg. 1972 Jul-Aug;51(4):647-55.

  PMID: 5064798 BACKGROUND

• Krestow M. The effect of post-anaesthetic dreaming on patient acceptance of ketamine anaesthesia: a comparison with thiopentone-nitrous oxide anaesthesia. Can Anaesth Soc J. 1974 Jul;21(4):385-9. doi: 10.1007/BF03006072. No abstract available.

  PMID: 4836917 BACKGROUND

• Freuchen I, Ostergaard J, Kuhl JB, Mikkelsen BO. Reduction of psychotomimetic side effects of Ketalar (ketamine) by Rohypnol (flunitrazepam). A randomized, double-blind trial. Acta Anaesthesiol Scand. 1976;20(2):97-103. doi: 10.1111/j.1399-6576.1976.tb05015.x.

  PMID: 7095 BACKGROUND

• Coad NR, Mills PJ, Verma R, Ramasubramanian R. Evaluation of blood loss during suction termination of pregnancy: ketamine compared with methohexitone. Acta Anaesthesiol Scand. 1986 Apr;30(3):253-5. doi: 10.1111/j.1399-6576.1986.tb02407.x.

  PMID: 3739583 BACKGROUND

• Renner RM, Jensen JT, Nichols MD, Edelman AB. Pain control in first-trimester surgical abortion: a systematic review of randomized controlled trials. Contraception. 2010 May;81(5):372-88. doi: 10.1016/j.contraception.2009.12.008. Epub 2010 Jan 27.

  PMID: 20399943 BACKGROUND

• Godwin SA, Burton JH, Gerardo CJ, Hatten BW, Mace SE, Silvers SM, Fesmire FM; American College of Emergency Physicians. Clinical policy: procedural sedation and analgesia in the emergency department. Ann Emerg Med. 2014 Feb;63(2):247-58.e18. doi: 10.1016/j.annemergmed.2013.10.015.

  PMID: 24438649 BACKGROUND

• Atkinson P, French J, Nice CA. Procedural sedation and analgesia for adults in the emergency department. BMJ. 2014 May 8;348:g2965. doi: 10.1136/bmj.g2965. No abstract available.

  PMID: 24812113 BACKGROUND

• Green SM, Roback MG, Kennedy RM, Krauss B. Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. Ann Emerg Med. 2011 May;57(5):449-61. doi: 10.1016/j.annemergmed.2010.11.030. Epub 2011 Jan 21.

  PMID: 21256625 BACKGROUND

• Newton A, Fitton L. Intravenous ketamine for adult procedural sedation in the emergency department: a prospective cohort study. Emerg Med J. 2008 Aug;25(8):498-501. doi: 10.1136/emj.2007.053421.

  PMID: 18660398 BACKGROUND

• Coralic Z, Sawe HR, Mfinanga JA, Cortez A, Koehl J, Siroker H, Reynolds TA. Ketamine procedural sedation in the emergency department of an urban tertiary hospital in Dar es Salaam, Tanzania. Emerg Med J. 2018 Apr;35(4):214-219. doi: 10.1136/emermed-2017-206974. Epub 2018 Jan 22.

  PMID: 29358491 BACKGROUND

• Bisanzo M, Nichols K, Hammerstedt H, Dreifuss B, Nelson SW, Chamberlain S, Kyomugisha F, Noble A, Arthur A, Thomas S. Nurse-administered ketamine sedation in an emergency department in rural Uganda. Ann Emerg Med. 2012 Apr;59(4):268-75. doi: 10.1016/j.annemergmed.2011.11.004. Epub 2011 Dec 9.

  PMID: 22169331 BACKGROUND

• Sacchetti A, Senula G, Strickland J, Dubin R. Procedural sedation in the community emergency department: initial results of the ProSCED registry. Acad Emerg Med. 2007 Jan;14(1):41-6. doi: 10.1197/j.aem.2006.05.023. Epub 2006 Aug 31.

  PMID: 16946280 BACKGROUND

• Allen RH, Singh R. Society of Family Planning clinical guidelines pain control in surgical abortion part 1 - local anesthesia and minimal sedation. Contraception. 2018 Jun;97(6):471-477. doi: 10.1016/j.contraception.2018.01.014. Epub 2018 Jan 31.

  PMID: 29407363 BACKGROUND

MeSH Terms

Interventions

Morphine; Fentanyl; Ketamine; Saline Solution

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Piperidines; Heterocyclic Compounds, 1-Ring; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Sophie Bussiere-Cote, MD

  Queen's University

  PRINCIPAL INVESTIGATOR

• Ashley Waddington, MD, MPA

  Queen's University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: For the three treatment arms, the nurses, the study participants, and the abortion provider will be blinded to study arm assignment and will remain blinded throughout the course of the study. As such, all study personnel who will be administering questionnaires will be appropriately blinded to minimize bias. The provider of the IV medications will not be blinded. This decision was made in order to ensure participant safety in titrating medication doses, and to avoid the need to unblind all members if a reversal agent is required. The provider of the anesthetic will not disclose which study arm the participant belongs to and will not be involved in administering questionnaires or data analysis.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This study will be a randomized, controlled, double-blinded, single-centre superiority trial with three parallel groups.

Study Record Dates

• First Submitted: November 20, 2018
• First Posted: November 23, 2018
• Study Start: June 10, 2019
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: September 8, 2022

Record last verified: 2022-09

Locations

CA (1)