Intravenous vs Oral Acetaminophen for Hip Fracture

(INTACT-HIP Trial)

Overseen By Aparna P Saripella

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University Health Network, Toronto

Disqualifiers: Neoplastic hip fracture, Severe cognitive impairment, Pre-existing delirium, Severe liver or kidney dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 3 days

42 Participants Needed

Trial Summary

What is the purpose of this 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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug acetaminophen for pain management?

Intravenous acetaminophen is effective for pain relief and reducing fever in both adults and children, as shown in clinical trials where it provided better pain relief than a placebo and reduced the need for additional pain medication. It is also comparable in effectiveness to other pain relief drugs like propacetamol and has been shown to decrease opioid usage in postsurgical pain management. ^{1 2 3 4 5}

Is acetaminophen safe for humans?

Acetaminophen (also known as paracetamol) is generally considered safe for humans when used as directed, with a low incidence of side effects. Minor effects like stomach upset and headache can occur, and overdose can lead to liver injury. A rare skin reaction called a fixed drug eruption has been reported. ^{6 7 8 9 10}

How does intravenous acetaminophen differ from oral acetaminophen for hip fracture pain management?

Intravenous acetaminophen is unique because it provides faster pain relief compared to oral acetaminophen due to its quicker absorption and higher plasma concentration, making it particularly useful in the immediate postoperative setting. Additionally, it may reduce the need for opioid medications, which can have more side effects. ^{2 3 11 12 13}

Research Team

Jean Wong, MD

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

This trial is for adults aged 60 and older who were walking unaided before suffering any type of non-cancerous hip fracture and are now undergoing inpatient surgery.

Inclusion Criteria

I am 60 years old or older.

I am having surgery that requires me to stay in the hospital.

I was walking on my own before my hip fracture, which wasn't caused by cancer.

Exclusion Criteria

I weigh less than 50kg.

Pre-existing delirium

I have a hip fracture caused by cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either intravenous (IV) acetaminophen or oral acetaminophen after hip fracture surgery

3 days

Daily monitoring during hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

1 visit (in-person) at 30 days post-surgery

Treatment Details

Interventions

• Acetaminophen

Trial Overview The INTACT-HIP study compares two ways to manage pain after hip surgery: one group gets IV acetaminophen with a fake pill, the other takes oral acetaminophen with a fake IV treatment. It's to see if this can be studied on a larger scale.

Participant Groups

Group I: Intravenous (IV) acetaminophen plus oral placebo Experimental Treatment 1 Intervention

In this group, the IV study drug will be IV acetaminophen and the oral study drug will be a placebo tablet.

Group II: Intravenous (IV) placebo plus oral acetaminophen Active Control 1 Intervention

In this group the IV study drug will be normal saline and the pill will be acetaminophen

Acetaminophen is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Tylenol for:

• Pain relief
• Fever reduction

Approved in European Union as Paracetamol for:

• Pain relief
• Fever reduction

Approved in Canada as Tylenol for:

• Pain relief
• Fever reduction

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

The new fast-dissolving acetaminophen tablet formulation (FD-APAP) disintegrates significantly faster than standard acetaminophen tablets, with a mean disintegration time of 12.9 minutes compared to 69.6 minutes (P < 0.0001).

FD-APAP also shows a quicker absorption rate, with a median time to peak concentration (Tmax) of 0.50 hours versus 0.67 hours for standard acetaminophen (P < 0.01), potentially leading to improved pain relief outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of a novel fast-dissolving acetaminophen tablet formulation (FD-APAP) and standard acetaminophen tablets using gamma scintigraphy and pharmacokinetic studies. Wilson, CG., Clarke, CP., Starkey, YY., et al.[2022]

Intravenous paracetamol (1 g) has been shown to provide significantly better pain relief than placebo in adults after surgeries, and it also reduces the need for opioid pain relief, making it an effective first-line treatment.

In pediatric patients, intravenous paracetamol (15 mg/kg) demonstrated similar pain relief and fever reduction compared to propacetamol (30 mg/kg), with a good safety profile and very rare adverse reactions (<1/10,000).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous paracetamol (acetaminophen). Duggan, ST., Scott, LJ.[2022]

Tramadol/paracetamol (TRM+P) has the highest reporting rate of adverse drug reactions (ADRs) among the three weak opioid analgesics studied, with a rate of 44.5 per 100,000 person-years, compared to 24.9 for dextropropoxyphene/paracetamol (DXP+P) and 12.5 for codeine/paracetamol (COD+P).

Dextropropoxyphene/paracetamol (DXP+P) is associated with a higher frequency of hepatobiliary ADRs and a worse safety profile compared to codeine/paracetamol (COD+P), despite having a lower overall reporting rate of ADRs than tramadol/paracetamol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reporting rate of adverse drug reactions to the French pharmacovigilance system with three step 2 analgesic drugs: dextropropoxyphene, tramadol and codeine (in combination with paracetamol). Tavassoli, N., Lapeyre-Mestre, M., Sommet, A., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Comparison of a novel fast-dissolving acetaminophen tablet formulation (FD-APAP) and standard acetaminophen tablets using gamma scintigraphy and pharmacokinetic studies. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Effects of single-dose injectable paracetamolversus propacetamol in pain management after minor gynecologic surgery: A multicenter, randomized, double-blind, active-controlled, two-parallel-group study. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Intravenous paracetamol (acetaminophen). [2022]

4. France pubmed.ncbi.nlm.nih.gov

The analgesic efficacy of an injectable prodrug of acetaminophen in children after orthopaedic surgery. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Randomized trial of OFIRMEV versus placebo for pain management after laparoscopic sleeve gastrectomy. [2017]

6. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of single and repeated administration of 1 gram intravenous acetaminophen injection (paracetamol) for pain management after major orthopedic surgery. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Cellulitis-like fixed drug eruption attributed to paracetamol (acetaminophen). [2013]

8. New Zealand pubmed.ncbi.nlm.nih.gov

The safety profile of sustained release paracetamol during therapeutic use and following overdose. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Reporting rate of adverse drug reactions to the French pharmacovigilance system with three step 2 analgesic drugs: dextropropoxyphene, tramadol and codeine (in combination with paracetamol). [2021]

10. England pubmed.ncbi.nlm.nih.gov

Current perceptions and use of paracetamol in dogs among veterinary surgeons working in the United Kingdom. [2023]

11. England pubmed.ncbi.nlm.nih.gov

A systematic review and trial sequential analysis of intravenous vs. oral peri-operative paracetamol. [2021]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Oral and Intravenous Paracetamol (Acetaminophen) When Co-Administered with Intravenous Morphine in Healthy Adult Subjects. [2021]

13. England pubmed.ncbi.nlm.nih.gov

Effect of intraoperative intravenous acetaminophen vs. intramuscular meperidine on pain and discharge time after paediatric dental restoration. [2022]