Intravenous vs Oral Acetaminophen in Postoperative Hip Fracture Adult Patients (INTACT-HIP)

INTACT-HIP: INTravenous Acetaminophen vs. Oral Randomized Controlled Trial in HIP Fracture Patients - a Feasibility Trial

The INTACT-HIP trial study will evaluate feasibility of conducting a randomized, double-blinded controlled trial comparing postoperative treatment with intravenous (IV) acetaminophen versus oral acetaminophen, in older adults undergoing hip fracture surgery.

The results of this feasibility trial will be used to inform designing a larger, multi-center, randomized controlled trial to assess the efficacy of IV acetaminophen compared to oral acetaminophen to reduce delirium and improve other clinical and patient-centered outcomes after hip fracture surgery. It will randomize 42 older adults to receive either oral or IV acetaminophen after hip fracture surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Surgery; Hip-fracture
• Intervention / Treatment: Drug: Intravenous (IV) acetaminophen + oral placebo; Drug: Intravenous (IV) placebo plus oral acetaminophen

• Study Type: Interventional
• Enrollment (Anticipated): 42
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Nayeemur Rahman; Phone Number: 3959 416-603-5800; Email: Nayeemur.Rahman@uhnresearch.ca
• Study Contact Backup: Name: Kawal P Singh; Phone Number: 3959 416-603-5800; Email: kawalpreet.singh@uhnresearcj.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 60 years of age and older
• Patients who were ambulating without human assistance before fracture, with any type of non-neoplastic hip fracture
• Patients undergoing surgical treatment as an inpatient

Exclusion Criteria:

• Patients with neoplastic hip fracture
• Severe cognitive impairment (Montreal Cognitive Assessment (MoCA) <10)
• Pre-existing delirium
• Known hypersensitivity or allergy to acetaminophen
• Severe or chronic liver or kidney dysfunction
• Planned postoperative ventilation
• Swallowing issues and/or dysphagia
• English language limitation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous (IV) acetaminophen plus oral placebo; In this group, the IV study drug will be IV acetaminophen and the oral study drug will be a placebo tablet.	Drug: Intravenous (IV) acetaminophen + oral placebo; Postoperatively patients will receive both a tablet and an IV solution every 6 hours for 48 hours, for a total of 8 doses. In this group, the IV study drug will be IV acetaminophen and the oral study drug will be a placebo tablet.
Active Comparator: Intravenous (IV) placebo plus oral acetaminophen; In this group the IV study drug will be normal saline and the pill will be acetaminophen	Drug: Intravenous (IV) placebo plus oral acetaminophen; Postoperatively patients will receive both a tablet and an IV solution every 6 hours for 48 hours, for a total of 8 doses. In this group the IV study drug will be normal saline and the pill will be acetaminophen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trial feasibility-Recruitment	Feasibility as assessed by recruitment rate. This will be assesses as proportion of patients enrolled in the study compared to the number of patients meeting the inclusion/exclusion criteria.	30 days
Trial feasibility-Attrition	Feasibility as assessed by attrition rates. This will be defined as the proportion of patients completing the study at follow-up compared to the enrolled patients.	30 days
Trial feasibility-Availability of human resources	Feasibility as assessed by lack of availability of human resources). Inability to include patient in study due to lack of pharmacist or research assistant availability will be documented.	30 days
Trial feasibility-Comply study procedures	Feasibility as assessed by failure to comply with study procedures. Failure to provide study drug at scheduled time will be documented.	30 days
Trial safety	Safety will be assessed as the number of participants experiencing intervention-related adverse or serious adverse events.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative pain	Pain will be assessed using the visual analogue (VAS) scale (0-10) at rest and movement, with 0=no pain and 10=worst pain possible	Before surgery, on day of surgery, and days 1,2,3 after surgery
Opioid consumption	Oral morphine equivalents (OMEQS) in milligrams	Before surgery, on day of surgery, and days 1,2,3 after surgery
Delirium	Delirium incidence will be measured using the Confusion assessment method (CAM)-Long Form	On day of surgery, and days 1,2, 3 after surgery
Cognitive dysfunction	Cognitive dysfunction will be assessed using the Montreal Cognitive Assessment (MoCA)	Before surgery and day 3 after surgery (or at discharge time if hospital stay less than 3 days after surgery)
Overall health and disability	Overall health and disability will be measured using the WHO Disability Assessment Schedule, version 2.0 (WHODAS 2.0), a 12-item validated measure that assesses cognition, mobility, self-care, interpersonal relationships, work and household roles, and participation in society	Baseline and at 30 days after surgery
Depression screen	Patient Health Questionnaire (PHQ)-2 a 2-question questionnaire will be used as a validated measure to screen for depression.	Before surgery and day 3 after surgery (or at discharge time if hospital stay less than 3 days after surgery)
Ambulation	Ambulation will be assessed as the ability to walk 10 feet or across a room without human assistance	Before surgery and day 3 after surgery (or at discharge time if hospital stay less than 3 days after surgery)
Post-operative adverse events	Post-operative adverse events will be obtained from the study institution's National Surgical Quality Improvement Project (NSQIP) database as as death, ICU admission, standardized cardiac, respiratory and neurological postoperative events, and readmission to hospital.	On day of surgery, days 1,2, 3 after surgery, and at 30 days after surgery
Discharge location	Location of discharge after surgery	At the time of discharge (at 1-3 days after surgery in most cases)

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Jean Wong, MD, University Health Network, Toronto

Publications and helpful links

General Publications

• Jahr JS, Breitmeyer JB, Pan C, Royal MA, Ang RY. Safety and efficacy of intravenous acetaminophen in the elderly after major orthopedic surgery: subset data analysis from 3, randomized, placebo-controlled trials. Am J Ther. 2012 Mar;19(2):66-75. doi: 10.1097/MJT.0b013e3182456810.
• Chen DX, Yang L, Ding L, Li SY, Qi YN, Li Q. Perioperative outcomes in geriatric patients undergoing hip fracture surgery with different anesthesia techniques: A systematic review and meta-analysis. Medicine (Baltimore). 2019 Dec;98(49):e18220. doi: 10.1097/MD.0000000000018220.
• Harris MJ, Brovman EY, Urman RD. Clinical predictors of postoperative delirium, functional status, and mortality in geriatric patients undergoing non-elective surgery for hip fracture. J Clin Anesth. 2019 Dec;58:61-71. doi: 10.1016/j.jclinane.2019.05.010. Epub 2019 May 14.

Study record dates

Study Major Dates

• Study Start (Anticipated): November 4, 2022
• Primary Completion (Anticipated): March 1, 2024
• Study Completion (Anticipated): June 1, 2024

Study Registration Dates

• First Submitted: May 16, 2022
• First Submitted That Met QC Criteria: June 15, 2022
• First Posted (Actual): June 21, 2022

Study Record Updates

• Last Update Posted (Actual): November 2, 2022
• Last Update Submitted That Met QC Criteria: October 31, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: elderly; acetaminophen; hip fracture surgery; oral vs intravenous
• Additional Relevant MeSH Terms: Wounds and Injuries; Leg Injuries; Femoral Fractures; Hip Injuries; Fractures, Bone; Hip Fractures; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: 21-5733

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No