Infections Joint ProstheticNCT05604157
Ancef Dosage in Knee Arthroplasty : Tourniquet Clinical Trial
A study testing Use of Tourniquet in people with Infections Joint Prosthetic, run by McGill University Health Centre/Research Institute of the McGill University Health Centre at 1 site in Canada.
Trial summary
Tourniquet inflation during total knee arthroplasty (TKA) is commonly used to reduce bleeding in the surgical field; thereby facilitating exposure and cementation. However, reducing circulation to the leg may also reduce antibiotic distribution to the peri-incisional tissues. Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Infections Joint Prosthetic
- What is being tested?
- Use of Tourniquet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteCanada
- Study dates
- 16 Sep 2021to 31 Dec 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adults ages 18-85 who require a primary total knee replacement
- Any gender
- Osteoarthritis, rheumatoid arthritis, avascular necrosis
Who cannot join
- Severe allergy to antibiotic used in the study
- Severe renal dysfunction (eGFR < 30 ml/min)
- Methicillin-resistant Staphylococcus aureus (MRSA) colonization
- participants who require revision surgery
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
Dr, Adam Hart
Montreal, Quebec, H3G 1A4
Adam Hart, MD, 514-934-1934 ext. 43040, adam.hart@mcgill.ca
Karen Smith, 514-934-1934 ext. 43040, karen.smith@muhc.mcgill.ca
About this study
Official title: Effect of Tourniquet on Local Tissue Concentrations of Cefazolin During Total Knee Arthroplasty: A Randomized Controlled Trial
Tourniquet inflation during total knee arthroplasty (TKA) is commonly used to reduce bleeding in the surgical field; thereby facilitating exposure and cementation. However, reducing circulation to the leg may also reduce antibiotic distribution to the peri-incisional tissues. Once inflated, further parenteral addition of antibiotics is not likely to achieve peak concentration. Some studies propose techniques of regional prophylaxis with a tourniquet to achieve higher cefazolin tissue concentrations. To our knowledge, the effect of tourniquet application on antibiotic tissue concentrations during total knee arthroplasty has not been explored. Furthermore, the effect of time from dose to incision, participants weight, and length of surgery on local tissue concentrations of Ancef are poorly understood. Considering that infections remain the leading source of early reoperation and revision surgery, insight and optimization of local tissue antibiotics is of paramount interest.
Read the detailed description
In Canada, over 130 000 cases of primary joint arthroplasty are performed annually, and this number is increasing steadily with the aging population. Projections from the United States estimate that, by 2030, more than 3.5 million primary joint arthroplasties will be performed annually. Although rare, with reported rates of 0.5-2% within 2 years, periprosthetic joint infection (PJI) is a devastating complication with serious morbidity. Effective use of antibiotic prophylaxis remains an important measure to prevent progression of an intraoperative contamination of the surgical site to an overt clinical infection. It creates a hostile environment in blood and tissue inhibiting pathogens that could contaminate the wound throughout the procedure. In order to be effective, the concentration of antibiotic must exceed the minimum inhibitory concentration (MIC) of the organism between skin incision and wound closure. S. aureus and Coagulase-negative staphylocci (CoNS), including S.epidermidis, cause close to half of deep infections and reported MIC ranges from 0.5 to 8 ug/ml in bone. Achieving fourfold MIC in tissue is recommended for halting the pathogen Cefazolin, efficient against most common pathogens in orthopaedics, has a good tissue penetration, minimal toxicity, low cost, and therefore is the antibiotic of choice in arthroplasty procedures. Pharmacokinetics studies have showed that Cefazolin achieves peak bone concentrations 40 minutes after parenteral application and based on systemic dosage methods, guidelines recommend that the antibiotic should be infused within 60 minutes before surgical incision. Compared to conventional systemic dosing, modern techniques using liquid chromatography and mass spectrometry can adequately measure antibiotic concentration in tissue like fat and bone.
- Conditions
- Infections Joint Prosthetic
- Being tested
- Use of Tourniquet
- Keywords
- Cefazolin, Tourniquet, Arthroplasty
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Use of TourniquetOther
Application of tourniquet or not in adults undergoing a primary total knee replacement.
| Study group | Role | What they receive |
|---|---|---|
| Tourniquet | Active comparator | 25 participants with tourniquet application Receives: Other: Use of Tourniquet |
| No tourniquet | No intervention | 25 participants without tourniquet application |
What is being measured
The primary outcome is the main question the study is designed to answer.
Local tissue concentrations of Cefazolin in serum, fat, synovium and bone
The principle intervention in this study will be the application of a tourniquet or no tourniquet during the procedure and its effect on local tissue concentrations of Cefazolin
Measured: Two years for study completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2022
- Study start16 Sep 2021
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Infections Joint ProstheticStudies of the same condition, open and under way.
- More trials run by McGill University Health Centre/Research Institute of the McGill University Health CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- McGill University Health Centre/Research Institute of the McGill University Health Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Adam Hart, McGill University Health Centre/Research Institute of the McGill University Health Centre
- Investigators
- Adam Hart, MD, Principal investigator, McGill University Health Centre/Research Institute of the McGill University Health Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05604157
- Sponsor's protocol ID
- 2021-6782
- Status last verified
- Nov 2022
- First submitted
- 22 Jun 2022
- Last updated
- 4 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am. 2007 Apr;89(4):780-5. doi: 10.2106/JBJS.F.00222.
PubMed 17403800Bosco JA, Bookman J, Slover J, Edusei E, Levine B. Principles of Antibiotic Prophylaxis in Total Joint Arthroplasty: Current Concepts. J Am Acad Orthop Surg. 2015 Aug;23(8):e27-35. doi: 10.5435/JAAOS-D-15-00017.
PubMed 26209148Fletcher N, Sofianos D, Berkes MB, Obremskey WT. Prevention of perioperative infection. J Bone Joint Surg Am. 2007 Jul;89(7):1605-18. doi: 10.2106/JBJS.F.00901. No abstract available.
PubMed 17606802Bicanic G, Crnogaca K, Barbaric K, Delimar D. Cefazolin should be administered maximum 30 min before incision in total knee arthroplasty when tourniquet is used. Med Hypotheses. 2014 Jun;82(6):766-8. doi: 10.1016/j.mehy.2014.03.020. Epub 2014 Mar 25.
PubMed 24717822Burke JF. The effective period of preventive antibiotic action in experimental incisions and dermal lesions. Surgery. 1961 Jul;50:161-8.
PubMed 16722001Yamada K, Matsumoto K, Tokimura F, Okazaki H, Tanaka S. Are bone and serum cefazolin concentrations adequate for antimicrobial prophylaxis? Clin Orthop Relat Res. 2011 Dec;469(12):3486-94. doi: 10.1007/s11999-011-2111-8. Epub 2011 Oct 4.
PubMed 21968901Young SW, Zhang M, Freeman JT, Vince KG, Coleman B. Higher cefazolin concentrations with intraosseous regional prophylaxis in TKA. Clin Orthop Relat Res. 2013 Jan;471(1):244-9. doi: 10.1007/s11999-012-2469-2.
PubMed 22773397Bhalodi AA, Housman ST, Shepard A, Nugent J, Nicolau DP. Tissue pharmacokinetics of cefazolin in patients with lower limb infections. Antimicrob Agents Chemother. 2013 Nov;57(11):5679-83. doi: 10.1128/AAC.01348-13. Epub 2013 Sep 16.
PubMed 24041887Quintiliani R, Nightingale C. Principles of antibiotic usage. Clin Orthop Relat Res. 1984 Nov;(190):31-5.
PubMed 6488647Prokuski L, Clyburn TA, Evans RP, Moucha CS. Prophylactic antibiotics in orthopaedic surgery. Instr Course Lect. 2011;60:545-55.
PubMed 21553797Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis. 1998 Jan;26(1):1-10; quiz 11-2. doi: 10.1086/516284.
PubMed 9455502Steinberg JP, Braun BI, Hellinger WC, Kusek L, Bozikis MR, Bush AJ, Dellinger EP, Burke JP, Simmons B, Kritchevsky SB; Trial to Reduce Antimicrobial Prophylaxis Errors (TRAPE) Study Group. Timing of antimicrobial prophylaxis and the risk of surgical site infections: results from the Trial to Reduce Antimicrobial Prophylaxis Errors. Ann Surg. 2009 Jul;250(1):10-6. doi: 10.1097/SLA.0b013e3181ad5fca.
PubMed 19561486Zhang M, Moore GA, Chin PKL, Everts R, Begg EJ. Simultaneous Determination of Cefalexin, Cefazolin, Flucloxacillin, and Probenecid by Liquid Chromatography-Tandem Mass Spectrometry for Total and Unbound Concentrations in Human Plasma. Ther Drug Monit. 2018 Dec;40(6):682-692. doi: 10.1097/FTD.0000000000000555.
PubMed 30015652Montreuil J, Tanzer M, Zhang YL, Rajda E, Avizonis D, Hart A. Tourniquet Use and Local Tissue Concentrations of Cefazolin During Total Knee Arthroplasty: A Randomized Clinical Trial. JAMA Netw Open. 2024 Aug 1;7(8):e2429702. doi: 10.1001/jamanetworkopen.2024.29702.
PubMed 39178000
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Tourniquet on Local Tissue Concentrations of Cefazolin During Total Knee Arthroplasty: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05604157
- Acronym / sponsor ID
- 2021-6782
- Conditions
- Infections Joint Prosthetic
- Keywords
- Cefazolin, Tourniquet, Arthroplasty
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- McGill University Health Centre/Research Institute of the McGill University Health CentreUniversity, hospital or other
- Study start
- 16 Sep 2021 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 3 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Tourniquet inflation during total knee arthroplasty (TKA) is commonly used to reduce bleeding in the surgical field; thereby facilitating exposure and cementation. However, reducing circulation to the leg may also reduce antibiotic distribution to the peri-incisional tissues. Once inflated, further parenteral addition of antibiotics is not likely to achieve peak concentration. Some studies propose techniques of regional prophylaxis with a tourniquet to achieve higher cefazolin tissue concentrations. To our knowledge, the effect of tourniquet application on antibiotic tissue concentrations during total knee arthroplasty has not been explored. Furthermore, the effect of time from dose to incision, participants weight, and length of surgery on local tissue concentrations of Ancef are poorly understood. Considering that infections remain the leading source of early reoperation and revision surgery, insight and optimization of local tissue antibiotics is of paramount interest.
Detailed description
In Canada, over 130 000 cases of primary joint arthroplasty are performed annually, and this number is increasing steadily with the aging population. Projections from the United States estimate that, by 2030, more than 3.5 million primary joint arthroplasties will be performed annually. Although rare, with reported rates of 0.5-2% within 2 years, periprosthetic joint infection (PJI) is a devastating complication with serious morbidity. Effective use of antibiotic prophylaxis remains an important measure to prevent progression of an intraoperative contamination of the surgical site to an overt clinical infection. It creates a hostile environment in blood and tissue inhibiting pathogens that could contaminate the wound throughout the procedure. In order to be effective, the concentration of antibiotic must exceed the minimum inhibitory concentration (MIC) of the organism between skin incision and wound closure. S. aureus and Coagulase-negative staphylocci (CoNS), including S.epidermidis, cause close to half of deep infections and reported MIC ranges from 0.5 to 8 ug/ml in bone. Achieving fourfold MIC in tissue is recommended for halting the pathogen Cefazolin, efficient against most common pathogens in orthopaedics, has a good tissue penetration, minimal toxicity, low cost, and therefore is the antibiotic of choice in arthroplasty procedures. Pharmacokinetics studies have showed that Cefazolin achieves peak bone concentrations 40 minutes after parenteral application and based on systemic dosage methods, guidelines recommend that the antibiotic should be infused within 60 minutes before surgical incision. Compared to conventional systemic dosing, modern techniques using liquid chromatography and mass spectrometry can adequately measure antibiotic concentration in tissue like fat and bone.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tourniquet | Active comparator | Other: Use of Tourniquet25 participants with tourniquet application |
| No tourniquet | No intervention | –25 participants without tourniquet application |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adults ages 18-85 who require a primary total knee replacement
- Any gender
- Osteoarthritis, rheumatoid arthritis, avascular necrosis
Key exclusion criteria (4 listed)
- Severe allergy to antibiotic used in the study
- Severe renal dysfunction (eGFR < 30 ml/min)
- Methicillin-resistant Staphylococcus aureus (MRSA) colonization
- participants who require revision surgery
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Use of TourniquetApplication of tourniquet or not in adults undergoing a primary total knee replacement. | Other | Tourniquet |
Primary outcome
Local tissue concentrations of Cefazolin in serum, fat, synovium and bone
Time frame: Two years for study completion
The principle intervention in this study will be the application of a tourniquet or no tourniquet during the procedure and its effect on local tissue concentrations of Cefazolin
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2022.
- Background: PubMed 17403800Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am. 2007 Apr;89(4):780-5. doi: 10.2106/JBJS.F.00222.
- Background: PubMed 26209148Bosco JA, Bookman J, Slover J, Edusei E, Levine B. Principles of Antibiotic Prophylaxis in Total Joint Arthroplasty: Current Concepts. J Am Acad Orthop Surg. 2015 Aug;23(8):e27-35. doi: 10.5435/JAAOS-D-15-00017.
- Background: PubMed 17606802Fletcher N, Sofianos D, Berkes MB, Obremskey WT. Prevention of perioperative infection. J Bone Joint Surg Am. 2007 Jul;89(7):1605-18. doi: 10.2106/JBJS.F.00901. No abstract available.
- Background: PubMed 24717822Bicanic G, Crnogaca K, Barbaric K, Delimar D. Cefazolin should be administered maximum 30 min before incision in total knee arthroplasty when tourniquet is used. Med Hypotheses. 2014 Jun;82(6):766-8. doi: 10.1016/j.mehy.2014.03.020. Epub 2014 Mar 25.
- Background: PubMed 16722001Burke JF. The effective period of preventive antibiotic action in experimental incisions and dermal lesions. Surgery. 1961 Jul;50:161-8.
- Background: PubMed 21968901Yamada K, Matsumoto K, Tokimura F, Okazaki H, Tanaka S. Are bone and serum cefazolin concentrations adequate for antimicrobial prophylaxis? Clin Orthop Relat Res. 2011 Dec;469(12):3486-94. doi: 10.1007/s11999-011-2111-8. Epub 2011 Oct 4.
- Background: PubMed 22773397Young SW, Zhang M, Freeman JT, Vince KG, Coleman B. Higher cefazolin concentrations with intraosseous regional prophylaxis in TKA. Clin Orthop Relat Res. 2013 Jan;471(1):244-9. doi: 10.1007/s11999-012-2469-2.
- Background: PubMed 24041887Bhalodi AA, Housman ST, Shepard A, Nugent J, Nicolau DP. Tissue pharmacokinetics of cefazolin in patients with lower limb infections. Antimicrob Agents Chemother. 2013 Nov;57(11):5679-83. doi: 10.1128/AAC.01348-13. Epub 2013 Sep 16.
- Background: PubMed 6488647Quintiliani R, Nightingale C. Principles of antibiotic usage. Clin Orthop Relat Res. 1984 Nov;(190):31-5.
- Background: PubMed 21553797Prokuski L, Clyburn TA, Evans RP, Moucha CS. Prophylactic antibiotics in orthopaedic surgery. Instr Course Lect. 2011;60:545-55.
- Background: PubMed 9455502Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis. 1998 Jan;26(1):1-10; quiz 11-2. doi: 10.1086/516284.
- Background: PubMed 19561486Steinberg JP, Braun BI, Hellinger WC, Kusek L, Bozikis MR, Bush AJ, Dellinger EP, Burke JP, Simmons B, Kritchevsky SB; Trial to Reduce Antimicrobial Prophylaxis Errors (TRAPE) Study Group. Timing of antimicrobial prophylaxis and the risk of surgical site infections: results from the Trial to Reduce Antimicrobial Prophylaxis Errors. Ann Surg. 2009 Jul;250(1):10-6. doi: 10.1097/SLA.0b013e3181ad5fca.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adam Hart, MD principal investigator
McGill University Health Centre/Research Institute of the McGill University Health Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Use of Tourniquet in people with Infections Joint Prosthetic, run by McGill University Health Centre/Research Institute of the McGill University Health Centre at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Adam Hart, MD (514-934-1934 ext. 43040, adam.hart@mgcill.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Local tissue concentrations of Cefazolin in serum, fat, synovium and bone (time frame: Two years for study completion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05604157, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2022.