Ignite Creation Date:
2024-05-06 @ 7:58 PM
Last Modification Date:
2024-10-26 @ 3:17 PM
Study NCT ID:
NCT06203769
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-01-12
First Post:
2023-11-29
Brief Title:
Reduction of Antibiotherapy Duration for Infections on Implantable Extra Cardiac Devices Leads
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Reduction of Antibiotherapy Duration for Infections on Implantable Extra Cardiac Devices Leads a Randomized Controlled Multicenter Non-inferiority Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
RAID
Brief Summary:
The design is an Open-label randomized controlled multicenter non-inferiority trial with blinded assessor which compares 2 antibiotic strategy 14-day antibiotic therapy after removal of infected material experimental group versus 28-day antibiotic therapy after removal of infected material control group
Randomization will be centralized individual 11 stratified on center and age 75 versus 75 years Analysis will be reported following CONSORT guidelines for pharmacological trials
Main analysis will be conducted according to per protocol and intent-to-treat principles Subgroup analysis will be conducted according to age classes of antibiotics at baseline and according to resistance testing and baseline renal clearance
Randomization will be centralized individual 11 stratified on center and age 75 versus 75 years Analysis will be reported following CONSORT guidelines for pharmacological trials
Main analysis will be conducted according to per protocol and intent-to-treat principles Subgroup analysis will be conducted according to age classes of antibiotics at baseline and according to resistance testing and baseline renal clearance
Detailed Description:
Infections of cardiac implantable electronic devices CIED are one of the most frequent complication after implantation of these devices with an incidence rate estimated at 482 1000 in Denmark mainly in the first year post implantation An american study found that the incidence of CIED infection in the USA increased from 153 in 2004 to 241 in 2008 and a National Inpatient Sample database study showed an increase from 145 to 341 P0001 from 2000 through 2012 These figures are constantly increasing and concern mostly older people
Although the mortality seems to be low compared to those of valvular infection evaluated at 4 for nonstaphylococcal infection and up to 9 for Staphylococcus aureus related infections those infections are responsible of numerous morbidities such as iterative hospitalizations decompensations of other comorbidities and autonomy loss especially for older people
Clinical presentations of CIED infections are varied and include generator pocket infections native or prosthetic CIED-associated valvular endocarditis CIED-IE with echocardiographic evidence of valve involvement and CIED lead infections CIED-LI with evidence of lead infection without valve involvement
In CIED infections removal of the device is the cornerstone of treatment and is usually required to enable cure in association with antimicrobial therapy for a few weeks However although antimicrobial therapy duration after removal of the device are relatively well defined for generator pocket infections 10 - 14 days for the remaining skin and soft tissue infection and CIED-IE 4 - 6 weeks the optimal duration of antibiotic treatment in CIED-LI has yet to be determined
Several series amalgamate generator pocket infection CIED-IE and CIED-LI descript duration of therapy and are therefore unhelpful in deciding on the optimum duration of antimicrobials
Guidelines for management of CIED infections recommend different durations of antibiotic treatment particularly for CIED-LI which can result in considerable inappropriate antimicrobial exposure in a vulnerable patient population
In light of the emergence of bacterial resistance and in order to limit the drug toxicities of antibiotics it is crucial to offer patients the shortest possible duration of treatment without losing efficiency
Infections of cardiac implantable electronic devices CIED are one of the most frequent complication after implantation of these devices with an incidence rate estimated at 482 1000 in Denmark mainly in the first year post implantation1 An american study found that the incidence of CIED infection in the USA increased from 153 in 2004 to 241 in 2008 and a National Inpatient Sample database study showed an increase from 145 to 341 P0001 from 2000 through 2012 These figures are constantly increasing and concern mostly older people
Although the mortality seems to be low compared to those of valvular infection evaluated at 4 for nonstaphylococcal infection and up to 9 for Staphylococcus aureus related infections 4 those infections are responsible of numerous morbidities such as iterative hospitalizations decompensations of other comorbidities and autonomy loss especially for older people
Clinical presentations of CIED infections are varied and include generator pocket infections native or prosthetic CIED-associated valvular endocarditis CIED-IE with echocardiographic evidence of valve involvement and CIED lead infections CIED-LI with evidence of lead infection without valve involvement
In CIED infections removal of the device is the cornerstone of treatment and is usually required to enable cure in association with antimicrobial therapy for a few weeks However although antimicrobial therapy duration after removal of the device are relatively well defined for generator pocket infections 10 - 14 days for the remaining skin and soft tissue infection and CIED-IE 4 - 6 weeks 5 the optimal duration of antibiotic treatment in CIED-LI has yet to be determined
Several series amalgamate generator pocket infection CIED-IE and CIED-LI descript duration of therapy and are therefore unhelpful in deciding on the optimum duration of antimicrobials
Guidelines for management of CIED infections recommend different durations of antibiotic treatment particularly for CIED-LI which can result in considerable inappropriate antimicrobial exposure in a vulnerable patient population
In light of the emergence of bacterial resistance and in order to limit the drug toxicities of antibiotics it is crucial to offer patients the shortest possible duration of treatment without losing efficiency
To this regard renal failure is one of the most frequent adverse effect during antibiotic treatment especially in older patients with polymedication and comorbidities and is responsible indirectly of increasing mortality
Furthermore shortening antibiotic therapy would allow to decrease the number of allergy events and Clostridium difficile colitis
In the most recent European recommendations if the TEE performed after device removal shows no signs of valve vegetation ie isolated lead vegetation the follow-up blood cultures are negative the clinical improvement is good and there are no pulmonary abscesses treatment duration for 2 weeks post-device extraction can be sufficient but total treatment duration should not be shorter than 4 weeks
Older US guidelines recommend at least 2 weeks of parenteral therapy after extraction of an infected device for patients with bloodstream infection Patients with sustained 24 hours positive blood cultures despite CIED removal and appropriate antimicrobial therapy should receive parenteral therapy for at least 4 weeks even if TEE is negative for valvular vegetations
In the British recommendations short course therapy 2 weeks could be considered if tricuspid valve is structurally normal no ghost lesions present after system removal on control TEE and rapid clinical response to device removal
Finally no clinical trial data are available to define the optimal duration of antimicrobial therapy for CIED-LI and all recommendations are based on retrospective studies and expert opinion US guidelines are mainly based on one retrospective non-randomized monocenter cohort study leading to possible confusion and indication bias However this study which is to our knowledge the only one on this topic 189 patients were included from 1991 to 2003 and presented either a generator pocket infections a CIED-IE or a CIED-LI without valvular infection All results were pooled together when describing duration of therapy and are therefore unhelpful in deciding on the optimum duration of antimicrobials Besides english recommendations are based on expert opinions themselves based on case series and pharmacological considerations
Our hypothesis is therefore that in CIED-LI 14 days of antimicrobial therapy after device extraction is sufficient regardless of the duration of previous antibiotic therapy if the bacteremia is controlled and if there are i no distant infectious foci abscess no valvular lesions
Therefore the benefit-risk balance of a shortening of antibiotic therapy for CIED infections needs to be assessed with a high-level of evidence
This study is endorsed by AEPEI
Although the mortality seems to be low compared to those of valvular infection evaluated at 4 for nonstaphylococcal infection and up to 9 for Staphylococcus aureus related infections those infections are responsible of numerous morbidities such as iterative hospitalizations decompensations of other comorbidities and autonomy loss especially for older people
Clinical presentations of CIED infections are varied and include generator pocket infections native or prosthetic CIED-associated valvular endocarditis CIED-IE with echocardiographic evidence of valve involvement and CIED lead infections CIED-LI with evidence of lead infection without valve involvement
In CIED infections removal of the device is the cornerstone of treatment and is usually required to enable cure in association with antimicrobial therapy for a few weeks However although antimicrobial therapy duration after removal of the device are relatively well defined for generator pocket infections 10 - 14 days for the remaining skin and soft tissue infection and CIED-IE 4 - 6 weeks the optimal duration of antibiotic treatment in CIED-LI has yet to be determined
Several series amalgamate generator pocket infection CIED-IE and CIED-LI descript duration of therapy and are therefore unhelpful in deciding on the optimum duration of antimicrobials
Guidelines for management of CIED infections recommend different durations of antibiotic treatment particularly for CIED-LI which can result in considerable inappropriate antimicrobial exposure in a vulnerable patient population
In light of the emergence of bacterial resistance and in order to limit the drug toxicities of antibiotics it is crucial to offer patients the shortest possible duration of treatment without losing efficiency
Infections of cardiac implantable electronic devices CIED are one of the most frequent complication after implantation of these devices with an incidence rate estimated at 482 1000 in Denmark mainly in the first year post implantation1 An american study found that the incidence of CIED infection in the USA increased from 153 in 2004 to 241 in 2008 and a National Inpatient Sample database study showed an increase from 145 to 341 P0001 from 2000 through 2012 These figures are constantly increasing and concern mostly older people
Although the mortality seems to be low compared to those of valvular infection evaluated at 4 for nonstaphylococcal infection and up to 9 for Staphylococcus aureus related infections 4 those infections are responsible of numerous morbidities such as iterative hospitalizations decompensations of other comorbidities and autonomy loss especially for older people
Clinical presentations of CIED infections are varied and include generator pocket infections native or prosthetic CIED-associated valvular endocarditis CIED-IE with echocardiographic evidence of valve involvement and CIED lead infections CIED-LI with evidence of lead infection without valve involvement
In CIED infections removal of the device is the cornerstone of treatment and is usually required to enable cure in association with antimicrobial therapy for a few weeks However although antimicrobial therapy duration after removal of the device are relatively well defined for generator pocket infections 10 - 14 days for the remaining skin and soft tissue infection and CIED-IE 4 - 6 weeks 5 the optimal duration of antibiotic treatment in CIED-LI has yet to be determined
Several series amalgamate generator pocket infection CIED-IE and CIED-LI descript duration of therapy and are therefore unhelpful in deciding on the optimum duration of antimicrobials
Guidelines for management of CIED infections recommend different durations of antibiotic treatment particularly for CIED-LI which can result in considerable inappropriate antimicrobial exposure in a vulnerable patient population
In light of the emergence of bacterial resistance and in order to limit the drug toxicities of antibiotics it is crucial to offer patients the shortest possible duration of treatment without losing efficiency
To this regard renal failure is one of the most frequent adverse effect during antibiotic treatment especially in older patients with polymedication and comorbidities and is responsible indirectly of increasing mortality
Furthermore shortening antibiotic therapy would allow to decrease the number of allergy events and Clostridium difficile colitis
In the most recent European recommendations if the TEE performed after device removal shows no signs of valve vegetation ie isolated lead vegetation the follow-up blood cultures are negative the clinical improvement is good and there are no pulmonary abscesses treatment duration for 2 weeks post-device extraction can be sufficient but total treatment duration should not be shorter than 4 weeks
Older US guidelines recommend at least 2 weeks of parenteral therapy after extraction of an infected device for patients with bloodstream infection Patients with sustained 24 hours positive blood cultures despite CIED removal and appropriate antimicrobial therapy should receive parenteral therapy for at least 4 weeks even if TEE is negative for valvular vegetations
In the British recommendations short course therapy 2 weeks could be considered if tricuspid valve is structurally normal no ghost lesions present after system removal on control TEE and rapid clinical response to device removal
Finally no clinical trial data are available to define the optimal duration of antimicrobial therapy for CIED-LI and all recommendations are based on retrospective studies and expert opinion US guidelines are mainly based on one retrospective non-randomized monocenter cohort study leading to possible confusion and indication bias However this study which is to our knowledge the only one on this topic 189 patients were included from 1991 to 2003 and presented either a generator pocket infections a CIED-IE or a CIED-LI without valvular infection All results were pooled together when describing duration of therapy and are therefore unhelpful in deciding on the optimum duration of antimicrobials Besides english recommendations are based on expert opinions themselves based on case series and pharmacological considerations
Our hypothesis is therefore that in CIED-LI 14 days of antimicrobial therapy after device extraction is sufficient regardless of the duration of previous antibiotic therapy if the bacteremia is controlled and if there are i no distant infectious foci abscess no valvular lesions
Therefore the benefit-risk balance of a shortening of antibiotic therapy for CIED infections needs to be assessed with a high-level of evidence
This study is endorsed by AEPEI
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None