Ignite Creation Date:
2024-05-06 @ 3:30 PM
Last Modification Date:
2024-10-26 @ 1:51 PM
Study NCT ID:
NCT04656184
Status:
RECRUITING
Last Update Posted:
2024-02-28
First Post:
2020-11-30
Brief Title:
A Trial Comparing the Efficacy and Safety of Anakinra Versus Intravenous Immunoglobulin IVIG Retreatment in Patients With Kawasaki Disease Who Failed to Respond to Initial Standard IVIG Treatment
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
A Randomized Phase III Multicenter Trial Comparing the Efficacy and Safety of Anakinra Versus Intravenous Immunoglobulin IVIG Retreatment in Patients With Kawasaki Disease Who Failed to Respond to Initial Standard IVIG Treatment
Status:
RECRUITING
Status Verified Date:
2024-02
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:
ANACOMP
Brief Summary:
Kawasaki disease KD is the most frequent vasculitis in younger children 5years and the first cause of acquired ischemic myocardiopathy in childhood Exceptionally KD may cause early death during the acute phase by myocardial infarction but may compromise the long-term cardiovascular outcome by accelerating atherosclerotic disease
The incidence of KD is high in far-Eastern countries and Hawaii but KD is relatively rare in other regions 10100000 children 5years in northern Europe which makes it difficult to develop research on these rare population
Early recognition and treatment by intravenous immunoglobulins IVIG influences the prognosis positively IVIG are the standard of care and decrease significantly the risk of coronary aneurysms However despite a first infusion of IVIG 20 of KD patients remain febrile and have high risk of coronary vasculitis Recent Japanese research group assessed additional cyclosporine treatment in first line KD treatment but failed preventing relapse To date there is no agreement for a more effective second line treatment
Based on the auto-inflammatory pattern of KD the investigators hypothesize that anti IL-1 blocking agents could bring a rapid and sustained effect on systemic and coronary inflammation in patients with KD
Our hypotheses are
1 Anakinra treatment may reduce the early and long-term mortality of patients with Kawasaki Disease KD by a rapid and sustained effect on vascular inflammation
2 The safety of anakinra is good as the drug has a very short half-life which allows its rapid withdrawal in case of serious adverse event
The use of anakinra is not associated with the risk of contamination by infectious agents which remain even minimal a possibility with the use of IVIG
The incidence of KD is high in far-Eastern countries and Hawaii but KD is relatively rare in other regions 10100000 children 5years in northern Europe which makes it difficult to develop research on these rare population
Early recognition and treatment by intravenous immunoglobulins IVIG influences the prognosis positively IVIG are the standard of care and decrease significantly the risk of coronary aneurysms However despite a first infusion of IVIG 20 of KD patients remain febrile and have high risk of coronary vasculitis Recent Japanese research group assessed additional cyclosporine treatment in first line KD treatment but failed preventing relapse To date there is no agreement for a more effective second line treatment
Based on the auto-inflammatory pattern of KD the investigators hypothesize that anti IL-1 blocking agents could bring a rapid and sustained effect on systemic and coronary inflammation in patients with KD
Our hypotheses are
1 Anakinra treatment may reduce the early and long-term mortality of patients with Kawasaki Disease KD by a rapid and sustained effect on vascular inflammation
2 The safety of anakinra is good as the drug has a very short half-life which allows its rapid withdrawal in case of serious adverse event
The use of anakinra is not associated with the risk of contamination by infectious agents which remain even minimal a possibility with the use of IVIG
Detailed Description:
It is a multicentric national randomized controlled parallel-group in a 11 ratio open labelled trial of superiority
The main objective is to compare the efficacy of Anakinra Interleukin 1 receptor type 1 - receptor antagonist with 2nd IVIG infusion in second line on fever in patients with KD who failed to respond to one infusion of IVIGstandard treatment
The main criterion-evaluating efficacy in both groups is the patient must reach a body axillary 05C tympanic oral temperature 38C within 2 days after initiation of treatment ie a binary outcome successfailure
The secondary objectives are to compare Anakinra with IVIG retreatment in terms of
Efficacy on fever at 72h
Efficacy on disease activity
Efficacy on KD symptoms
Efficacy on coronary lesions eg dilatation and aneurysm
Efficacy on inflammation
Safety and tolerability Secondary End Points linked with the secondary objectives
To compare Anakinra with IVIG retreatment in terms of
Temperature 38C within 3 days 72h after initiation of treatment
Decrease of the CRP values from baseline to day 30CRP6 mgL at day 30
Reduction in physician assessment of disease activity on a 10 points scale of at least to 50 between baseline and day 14
Reduction in patients parents assessment of disease activity on a 10 points scale of to at least 50 between baseline and day 14
Resolution of coronary abnormalities ie worst Z score 25 by echocardiogram if present at day 45
Adverse events painredness at injection site bacterial infection hepatitis macrophage activation syndrome severe neutropenia
Monitoring of adverse events
Physical examination Complete clinical exam will be performed at each visit to detect symptoms of KD rash cervical nodes mucous lesions extremities GI pulmonary cardio vascular neurologic and muscularjoint evaluation and possible associated morbidity eg concomitant infection
Local tolerability of injections will be evaluated by physician from V2 to V8 pain redness swelling induration itching haemorrhage and quoted from none mild moderate severe
Vital signs and body measurements at each visit V1 to V9 The body temperature will be measured daily until d30 Parents will receive a follow-up booklet
Laboratory evaluations hematologic hepatic and renal assessment will be followed
Group 1 KINERET
KINERET in the form of prefilled syringe with 100 mg of anakinra per 067 ml 150 mgmL and adapted to paediatric population in pack sizes of 7 Patients in group I will receive a starting dose of anakinra is 4 mgkg at visit D1 or day 0 if possible During visits D1 and D2 if patients are still febrile with 12 hours H12 of treatment they will receive a supplementary dose of 2 mgKg otherwise they will remain at a starting dose of 4mgkg If they are still febrile at H24 they will receive a dose of 8mgkg otherwise they will maintain their dose of 6 mgkg Patients with temperature 38C at any point between initiation and day 14 but who develop secondary fever due to KD could have further escalation dose of anakinra until a maximum dose of 8mgKg
Group 2 IVIG Immunoglobulins concentrates used for the ANACOMP study should be preferably the specialty PRIVIGEN 100mgmL 10g of human immunoglobulins solute for intravenous infusion manufactured by CSL Behring Commonwealth Serum Laboratories Other presentations in mL 25 50 200 400 exist corresponding to respectively 25g 5g 20 and 40g of immunoglobulins Patients in group II will receive one infusion of 2gkg of intravenous Immunoglobulins at visit D1 or day 0 if possible
The main objective is to compare the efficacy of Anakinra Interleukin 1 receptor type 1 - receptor antagonist with 2nd IVIG infusion in second line on fever in patients with KD who failed to respond to one infusion of IVIGstandard treatment
The main criterion-evaluating efficacy in both groups is the patient must reach a body axillary 05C tympanic oral temperature 38C within 2 days after initiation of treatment ie a binary outcome successfailure
The secondary objectives are to compare Anakinra with IVIG retreatment in terms of
Efficacy on fever at 72h
Efficacy on disease activity
Efficacy on KD symptoms
Efficacy on coronary lesions eg dilatation and aneurysm
Efficacy on inflammation
Safety and tolerability Secondary End Points linked with the secondary objectives
To compare Anakinra with IVIG retreatment in terms of
Temperature 38C within 3 days 72h after initiation of treatment
Decrease of the CRP values from baseline to day 30CRP6 mgL at day 30
Reduction in physician assessment of disease activity on a 10 points scale of at least to 50 between baseline and day 14
Reduction in patients parents assessment of disease activity on a 10 points scale of to at least 50 between baseline and day 14
Resolution of coronary abnormalities ie worst Z score 25 by echocardiogram if present at day 45
Adverse events painredness at injection site bacterial infection hepatitis macrophage activation syndrome severe neutropenia
Monitoring of adverse events
Physical examination Complete clinical exam will be performed at each visit to detect symptoms of KD rash cervical nodes mucous lesions extremities GI pulmonary cardio vascular neurologic and muscularjoint evaluation and possible associated morbidity eg concomitant infection
Local tolerability of injections will be evaluated by physician from V2 to V8 pain redness swelling induration itching haemorrhage and quoted from none mild moderate severe
Vital signs and body measurements at each visit V1 to V9 The body temperature will be measured daily until d30 Parents will receive a follow-up booklet
Laboratory evaluations hematologic hepatic and renal assessment will be followed
Group 1 KINERET
KINERET in the form of prefilled syringe with 100 mg of anakinra per 067 ml 150 mgmL and adapted to paediatric population in pack sizes of 7 Patients in group I will receive a starting dose of anakinra is 4 mgkg at visit D1 or day 0 if possible During visits D1 and D2 if patients are still febrile with 12 hours H12 of treatment they will receive a supplementary dose of 2 mgKg otherwise they will remain at a starting dose of 4mgkg If they are still febrile at H24 they will receive a dose of 8mgkg otherwise they will maintain their dose of 6 mgkg Patients with temperature 38C at any point between initiation and day 14 but who develop secondary fever due to KD could have further escalation dose of anakinra until a maximum dose of 8mgKg
Group 2 IVIG Immunoglobulins concentrates used for the ANACOMP study should be preferably the specialty PRIVIGEN 100mgmL 10g of human immunoglobulins solute for intravenous infusion manufactured by CSL Behring Commonwealth Serum Laboratories Other presentations in mL 25 50 200 400 exist corresponding to respectively 25g 5g 20 and 40g of immunoglobulins Patients in group II will receive one infusion of 2gkg of intravenous Immunoglobulins at visit D1 or day 0 if possible
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