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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare the effectiveness of intravenous (IV) versus oral acetaminophen (also known as paracetamol or Tylenol) in older adults recovering from hip fracture surgery. Researchers seek to determine if one method better reduces delirium and improves recovery outcomes. Participants will be randomly assigned to receive either IV acetaminophen with a placebo pill or oral acetaminophen with an IV placebo. Individuals who walked independently before the fracture and are undergoing surgery for a non-cancerous hip fracture may be eligible to join. As a Phase 4 trial, this study involves an FDA-approved treatment and aims to understand its benefits for more patients.

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 is the safety track record for acetaminophen?

Research has shown that acetaminophen, whether administered through an IV or as a pill, is safe for post-surgery use. Studies have found that both forms can reduce pain and lessen the need for stronger painkillers. Specifically, using IV acetaminophen has been linked to lower pain levels and reduced opioid use (strong painkillers that can be addictive) after hip surgery. Additionally, acetaminophen, whether taken orally or through an IV, is generally well-tolerated by patients. These studies have reported no major safety concerns for either method. Overall, the evidence supports the safety of both IV and oral acetaminophen for managing post-surgery pain. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike standard treatments for hip fractures, which typically rely on oral acetaminophen or other oral pain medications, this trial explores intravenous (IV) administration of acetaminophen. Researchers are excited about IV acetaminophen because it might offer faster pain relief than oral options, as it bypasses the digestive system and enters the bloodstream directly. This could be particularly beneficial for patients who have difficulty swallowing or need immediate pain control. Additionally, the trial compares IV acetaminophen to oral acetaminophen to determine which is more effective, potentially leading to improved pain management strategies for hip fracture patients.

What evidence suggests that this trial's treatments could be effective for hip fracture surgery?

Research shows that administering acetaminophen through an IV can help manage pain in patients with hip fractures. In this trial, some participants will receive intravenous (IV) acetaminophen along with an oral placebo. Studies have found that IV acetaminophen can lead to better pain relief and reduce the need for strong painkillers like opioids. This means patients might experience less pain and require fewer additional medications. Although data is limited, some evidence suggests that IV acetaminophen can help older adults leave the hospital sooner after hip surgery. This treatment has proven effective in similar situations, indicating it could benefit recovery from a hip fracture. ^{1 2 3 6 7}

Who Is on the Research Team?

Jean Wong, MD

Principal Investigator

University Health Network, Toronto

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4536513/

Is Scheduled Intravenous Acetaminophen Effective in the ... Conclusion: The utilization of scheduled IV acetaminophen as part of a standardized pain management protocol for geriatric hip fractures resulted in shortened ...

2. link.springer.com link.springer.com/article/10.1007/s12630-022-02257-6

Effect of intravenous acetaminophen on postoperative ... There is very limited low-level evidence that iv acetaminophen improves preoperative and postoperative analgesia and shortens hospital stay in older hip ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35534770/

Effect of intravenous acetaminophen on postoperative ... There is very limited low-level evidence that iv acetaminophen improves preoperative and postoperative analgesia and shortens hospital stay in older hip ...

4. josr-online.biomedcentral.com josr-online.biomedcentral.com/articles/10.1186/s13018-023-04328-w

Outcomes of hip fracture treatment with intravenous morphine ... Protocols involving intravenous acetaminophen have been shown to result in significant improvement in pain scores, reduction in opioid use, ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0020138319301056

Comparison of the postoperative analgesic efficacies ... A RCT was conducted to compare the postoperative analgesic efficacy of intravenous acetaminophen and FICB in hip fracture patients.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0883540320305775

The Efficacy and Safety of Acetaminophen in Total Joint ... Oral and IV acetaminophen demonstrates the ability to safely reduce postoperative pain and opioid consumption during the inpatient hospital stay.

7. signavitae.com signavitae.com/articles/10.22514/sv.2023.052

Oral vs. IV paracetamol for pain control in patients with ... The treatment with paracetamol 1000 mg IV and OR resulted effective and safe for patients with FF waiting for surgery.