Delirium in Elderly Patients With Trauma of the Hip

NCT ID: NCT02689024

Last Updated: 2023-08-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE4

Total Enrollment

239 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-05-31

Study Completion Date

2023-07-19

Brief Summary

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A broken hip occurs frequently in elderly patients and is often very painful. Side effects of inadequately treated pain as well as the traditional drugs (administered through intravenous catheter) used to treat pain are, among others, a confusional state, called delirium. When pain medication is administered locally, only around the hip joint, pain might be treated more effectively and these side effects could be prevented. This is called a nerve block.

The current study evaluates the use of a continuous nerve block throughout the complete hospital admission with a catheter around the hip joint versus the use of traditionally used pain medication administered though an intravenous catheter in elderly patients with a broken hip. Half of all patients will receive the nerve block while in the emergency department and the other half will receive pain medication through the intravenous access.

Detailed Description

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BACKGROUND Hip fractures occur frequently and are usually very painful. Pain itself is an indicator for increased risk of complications. A significant complication is delirium, occurring in up to 25% of all elderly patients with hip fractures. For a large proportion, triggers for development of delirium reaches back to the preoperative phase, where polypharmacy (including opioid use) and inadequately treated pain are major risk factors. Delirium is associated with negative health consequences, increased hospital stay, falls, higher mortality, decreased physical and cognitive function, re-hospitalization, increased risk of dementia and increased societal costs. Therefore, pain should be optimally treated as soon as possible, however the elderly patient poses a challenge in good pain treatment, because of physiological age-related changes, different drug effects, distribution, metabolism and elimination. Opioids frequently lead to respiratory depression, hypotension, nausea/vomiting and sedation in this vulnerable patient group. As a consequence, these drugs are often under dosed and pain treated insufficiently. Besides, drugs as opioids and NSAIDs have been associated with an increased delirium risk. A nerve block could alleviate these clinical issues.

An example of a nerve block frequently utilized in the Emergency Department (ED) is a Fascia Iliaca Compartment Block (FICB), in which local anesthetics are injected underneath the pelvic iliac fascia in order to block femoral, obturator and lateral cutaneous nerves to provide anesthesia of hip, thigh and knee. Case-series and historically controlled cohort studies show a single-shot FICB is a rapid, safe and easy procedure providing excellent analgesia, decreased opioid need and little risk of complications. Delirium as outcome was reported in one RCT; a decreased delirium incidence after using repetitive, blind, single-shot FICBs (not in the acute setting) with pethidine (with increased intrinsic risk of developing delirium) as comparison. In order to prevent the need for repetitive insertions, leaving a catheter would create a route in order to provide continuous analgesia with local anesthetics. Two case series describe this continuous FICB in hip fractures and reported good pain control and decreased length of hospital stay without any infectious complications. No comparison studies have been done with a continuous FICB.

The objective of the current study is to investigate whether the use of a continuous FICB, started early (in the ED) and continued throughout the complete clinical course of a hip fracture, will decrease occurrence of delirium in elderly patients with hip fractures.

METHODS This study is designed as a prospective, open, multi-center, randomized interventional trial. Patients will be allocated to continuous FICB or care as usual (according to national guidelines) in a 1:1 ratio and followed up until three months after hospital discharge.

SAMPLE SIZE AND DATA ANALYSIS The primary outcome (occurrence of delirium) is expected to be distributed normally. Although evidence to prevent delirium is scarce, an absolute reduction of 13% incidence has been reported previously after an intervention. The estimated delirium incidence according to literature is 25%. The hypothesis is that by using a continuous FICB administered very early in the clinical course in the ED, the incidence can be decreased from 25 to 12%. Superiority of the FICB versus usual care will be tested using the Chi Square Test. In order to detect a clinically relevant between-group-difference of 13% decrease in incidence, a significance level of 0.05 and 80% power will be used. For this analysis, each group will have 154 patients. When accounting for 10% loss to follow-up after three months, a total study population of 340 will be needed.

The primary analysis will be based on the intention to treat principle. Per protocol analysis will be performed to check robustness of results. Baseline characteristics will be presented using descriptive statistics. Ordinal data will be analyzed using Chi Square Test or Fisher exact test. Continuous data will be assessed by a Student's t-test if normally distributed or Mann Whitney U test if otherwise. Missing data will be corrected by multiple imputation.

An economic evaluation will be performed focusing on possible gained benefits of pain management with a continuous FICB compared to care as usual and the related health care costs. The economic evaluation will be performed from a societal perspective with a time horizon of three months and capturing the value of all resources utilized. The economic evaluation will be set up as a Cost-Effectiveness Analysis (CEA). Besides a CEA, a Budget Impact Analysis (BIA) will be performed according to the ISPOR Task Force principles.

Conditions

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Hip Fractures Anesthesia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Continuous FICB with local anesthetics

With ultrasound guidance, a Fascia Iliaca Compartment Block will be administered and a catheter left in the compartment underneath the iliac fascia. This catheter will remain in place until two days after surgery.

Initial pain treatment in the Emergency Department will be with 40 mL bupivacaine 0.25% or equipotent dosages of levobupivacaine or ropivacaine. Thereafter, until removal of the catheter, pain is treated by titrating local anesthetics according to pain scores.

Group Type EXPERIMENTAL

Bupivacaine

Intervention Type DRUG

Local anesthetic: amide group ATC code N01BB01

Levobupivacaine

Intervention Type DRUG

Local anesthetic: amide group ATC code N01BB10

Ropivacaine

Intervention Type DRUG

Local anesthetic: amide group ATC code N01BB09

Traditional care with systemic analgesia

Traditional care (usual care) will be on the discretion of the treating physician or hospital protocols and will comprise of systemic opioids such as fentanyl or morphine.

Usually, these opioids are combined with several other drugs, such as: paracetamol, NSAIDs (diclofenac or ibuprofen or naproxen) or dipyrone. (Inter)national guidelines advice morphine as first line agent in elderly patients with hip fractures, as longer acting analgesics are usually required.

Group Type ACTIVE_COMPARATOR

Acetaminophen

Intervention Type DRUG

Analgesic drug: Acetanilide derivate with analgetic and antipyretic properties ATC code N02BE01

Diclofenac

Intervention Type DRUG

Non-Steroidal Anti-Inflammatory Drug: Acetic acid derivative ATC code M01AB05 Usual dosage is 50 mg t.i.d. orally or 75 mg b.i.d. intramuscularly. In the Netherlands, intravenous administration is not used.

Ibuprofen

Intervention Type DRUG

Non-Steroidal Anti-Inflammatory Drug: Propionic acid derivative ATC code M01AE01 Usual dosage is 400 mg t.i.d. or q.i.d. orally.

Naproxen

Intervention Type DRUG

Non-Steroidal Anti-Inflammatory Drug: Propionic acid derivative ATC code M01AE02 Usual dosage is initially 500 mg orally, followed by 250 mg b.i.d. or t.i.d.

Dipyrone

Intervention Type DRUG

Analgesic drug: Pyrazolone derivate with analgetic, antipyretic and antiphlogistic properties ATC N02BB02 Usual dosage is 1000 mg t.i.d. or q.i.d. orally and intravenously

Fentanyl

Intervention Type DRUG

Opioids: Phenylpiperidine derivative. Short-acting opioid. ATC code N02AB03 Usual dosage is 1 ug/kg intravenously and titrated guided by pain scores and possible side effects. Above the age of 60, dosages are usually divided in two in order to prevent adverse events.

Morphine

Intervention Type DRUG

Opioids: Natural opium alkaloid. Longer-acting opioid. ATC code N02AA01 Usual dosage is 0.1 mg intravenously and titrated guided by pain and possible side effects. Above the age of 60, dosages are usually divided in two in order to prevent adverse events.

Interventions

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Bupivacaine

Local anesthetic: amide group ATC code N01BB01

Intervention Type DRUG

Acetaminophen

Analgesic drug: Acetanilide derivate with analgetic and antipyretic properties ATC code N02BE01

Intervention Type DRUG

Diclofenac

Non-Steroidal Anti-Inflammatory Drug: Acetic acid derivative ATC code M01AB05 Usual dosage is 50 mg t.i.d. orally or 75 mg b.i.d. intramuscularly. In the Netherlands, intravenous administration is not used.

Intervention Type DRUG

Ibuprofen

Non-Steroidal Anti-Inflammatory Drug: Propionic acid derivative ATC code M01AE01 Usual dosage is 400 mg t.i.d. or q.i.d. orally.

Intervention Type DRUG

Naproxen

Non-Steroidal Anti-Inflammatory Drug: Propionic acid derivative ATC code M01AE02 Usual dosage is initially 500 mg orally, followed by 250 mg b.i.d. or t.i.d.

Intervention Type DRUG

Dipyrone

Analgesic drug: Pyrazolone derivate with analgetic, antipyretic and antiphlogistic properties ATC N02BB02 Usual dosage is 1000 mg t.i.d. or q.i.d. orally and intravenously

Intervention Type DRUG

Fentanyl

Opioids: Phenylpiperidine derivative. Short-acting opioid. ATC code N02AB03 Usual dosage is 1 ug/kg intravenously and titrated guided by pain scores and possible side effects. Above the age of 60, dosages are usually divided in two in order to prevent adverse events.

Intervention Type DRUG

Morphine

Opioids: Natural opium alkaloid. Longer-acting opioid. ATC code N02AA01 Usual dosage is 0.1 mg intravenously and titrated guided by pain and possible side effects. Above the age of 60, dosages are usually divided in two in order to prevent adverse events.

Intervention Type DRUG

Levobupivacaine

Local anesthetic: amide group ATC code N01BB10

Intervention Type DRUG

Ropivacaine

Local anesthetic: amide group ATC code N01BB09

Intervention Type DRUG

Other Intervention Names

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Marcaine Paracetamol Metamizole, Novalgin Chirocaine Naropin

Eligibility Criteria

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Inclusion Criteria

* adult patients aged ≥ 55 years with
* a radiographically confirmed hip fracture

Exclusion Criteria

* multiple injuries (polytrauma patients)
* previous adverse reaction or known allergy to local anaesthetics or opioids or paracetamol
* skin infection in proximity of injection site
* delirious state at presentation in the ED
Minimum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role lead

Responsible Party

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Milan Ridderikhof

MD PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Markus Hollmann, MD, PhD, PhD

Role: PRINCIPAL_INVESTIGATOR

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Locations

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Tergooi Ziekenhuis

Hilversum, North Holland, Netherlands

Site Status

Meander Medical Center

Amersfoort, , Netherlands

Site Status

Slotervaart Medical Center

Amsterdam, , Netherlands

Site Status

VU Medical Center

Amsterdam, , Netherlands

Site Status

Academic Medical Center

Amsterdam, , Netherlands

Site Status

Countries

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Netherlands

References

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Morrison RS, Magaziner J, Gilbert M, Koval KJ, McLaughlin MA, Orosz G, Strauss E, Siu AL. Relationship between pain and opioid analgesics on the development of delirium following hip fracture. J Gerontol A Biol Sci Med Sci. 2003 Jan;58(1):76-81. doi: 10.1093/gerona/58.1.m76.

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Leslie DL, Zhang Y, Holford TR, Bogardus ST, Leo-Summers LS, Inouye SK. Premature death associated with delirium at 1-year follow-up. Arch Intern Med. 2005 Jul 25;165(14):1657-62. doi: 10.1001/archinte.165.14.1657.

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Reference Type BACKGROUND
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Guay J, Kopp S. Peripheral nerve blocks for hip fractures in adults. Cochrane Database Syst Rev. 2020 Nov 25;11(11):CD001159. doi: 10.1002/14651858.CD001159.pub3.

Reference Type DERIVED
PMID: 33238043 (View on PubMed)

Related Links

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Other Identifiers

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2015-003650-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NL54580.018.15

Identifier Type: -

Identifier Source: org_study_id

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