Ignite Creation Date:
2024-05-06 @ 3:51 PM
Last Modification Date:
2024-10-26 @ 1:58 PM
Study NCT ID:
NCT04784988
Status:
COMPLETED
Last Update Posted:
2024-03-27
First Post:
2021-02-09
Brief Title:
Intensive Replacement Treatment in Haemophilia Patients With Synovitis
Sponsor:
Federico II University
Organization:
Federico II University
Study Overview
Official Title:
Intensive Replacement Treatment in Haemophilia Patients With Synovitis
Status:
COMPLETED
Status Verified Date:
2024-03
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:
None
Brief Summary:
Background Joint haemorrhage represents the most common type of bleeding episode in persons with hemophilia PwH In the absence of an adequate prophylaxis with Factor VIII for hemophilia A or FIX for hemophilia B concentrates up to 85 of patients with severe hemophilia develop a clinically overt joint disease Screening of early signs of arthropathy is needed Synovitis is widely considered as one of the parameters to be taken into account for the diagnosis and the surveillance of joint impairment in PwH
Aim To assess if an intensive factor VIII replacement treatment is able at reverting synovitis in PwH
Methods The present study is a randomized open-label cross-over study Among patients referred to enrolling Haemophilia Centres consecutive patients with severe FVIII 1 or severe-moderate FVIII 2 haemophilia A without inhibitors will be enrolled The present study will be organized in 2 phases
Phase 1 US screening All patients will undergo an ultrasound examination of elbows ankles and knees to define joint status and to identify presenceabsence of synovitis according to the HEAD-US system
Phase 2 Intervention Patients with US evidence of synovitis will be randomly assigned at undergoing a PK assessment with my-PK-fit to start a prophylaxis with Adynovi targeting a 12 FVIII through level PROPEL-like arm or to continue ongoing standard treatment control arm US examination of the six joints will be repeated monthly for six months and in case of onset of symptoms that might suggest an acute bleeding episode After six months the two treatment arm will be switched in the frame of a cross-over approach and all PwH will be followed for other 6 months The primary outcome will be represented by changes in synovial status during the intensive factor VIII replacement treatment vs standard treatment
Aim To assess if an intensive factor VIII replacement treatment is able at reverting synovitis in PwH
Methods The present study is a randomized open-label cross-over study Among patients referred to enrolling Haemophilia Centres consecutive patients with severe FVIII 1 or severe-moderate FVIII 2 haemophilia A without inhibitors will be enrolled The present study will be organized in 2 phases
Phase 1 US screening All patients will undergo an ultrasound examination of elbows ankles and knees to define joint status and to identify presenceabsence of synovitis according to the HEAD-US system
Phase 2 Intervention Patients with US evidence of synovitis will be randomly assigned at undergoing a PK assessment with my-PK-fit to start a prophylaxis with Adynovi targeting a 12 FVIII through level PROPEL-like arm or to continue ongoing standard treatment control arm US examination of the six joints will be repeated monthly for six months and in case of onset of symptoms that might suggest an acute bleeding episode After six months the two treatment arm will be switched in the frame of a cross-over approach and all PwH will be followed for other 6 months The primary outcome will be represented by changes in synovial status during the intensive factor VIII replacement treatment vs standard treatment
Detailed Description:
Joint haemorrhage represents the most common type of bleeding episode in persons with hemophilia PwH and recurrent hemarthrosis triggers chronic arthropathy which is the most frequent chronic complication in hemophilia patients In the absence of an adequate prophylaxis age at start regimen duration adherence with Factor VIII for hemophilia A or FIX for hemophilia B concentrates up to 85 of patients with severe hemophilia develop a clinically overt joint disease
On the other hand some recent data suggest that despite adequate prophylaxis a not negligible percentage of PwH develop arthropathy
Thus an adequate screening of early signs of arthropathy is needed On this hand synovitis is widely considered as one of the parameters to be taken into account for the diagnosis and the surveillance of joint impairment in PwH Synovitis represents a key feature potentially related to under-treatment due to insufficient therapy regimens or to a limited compliance to treatment to pharmacokinetics variability or to demanding dailysport activities Accordingly there is a general agreement on the indication to consider the presence of synovitis as a marker of disease activity in PwH
MATERIALS AND METHODS
Among patients referred to enrolling Haemophilia Centres to be defined consecutive patients with severe FVIII 1 or severe-moderate FVIII 2 haemophilia A without inhibitors will be enrolled according to the above reported inclusion and exclusion criteria For each subject a trained staff will record demographic data including age race ethnicity body mass index BMI kgm2 Information from medical records will also include the number of bleeding episodes and the amount of factor concentrate used during the previous 12 months for regular prophylaxis and for breakthrough bleeding episodes treatment The present study will be organized in 2 phases
Phase 1 US screening All patients will undergo an ultrasound examination of elbows ankles and knees to define joint status and to define presenceabsence of synovitis according to the HEAD-US system Synovitis screening protocol will include examination of the olecranon recess elbow suprapatellar recess knee and anterior recess of the tibiotalar joint ankle For a detailed scanning protocol see Figure 1 Synovitis will be scored as absentminimal score 0 mildmoderate score 1 and severe score 2
Phase 2 Intervention Patients with US evidence of synovitis will be randomly assigned at undergoing a PK assessment with WAPPS-Hemo to start a prophylaxis with any EHL-FVIII targeting a 12 FVIII through level PROPEL-like arm or to continue ongoing standard treatment control arm US examination of the six joints will be repeated monthly for six months and in case of onset of symptoms that might suggest an acute bleeding episode For both treatment arms changes in synovitis status the number of bleeding episodes number of infusions and FVIII consumption will be recorded In case of confirmed hemarthrosis an intensive treatment will be started with the ongoing treatment according to current guidelines During the intensive treatment period the US assessment of the affected joint will be repeated every 7 days The intensive replacement treatment will be stopped when US will demonstrate complete resolution of intra-articular bleeding The time to pain disappearance the time to US evidence of bleeding resolution and the number and doses infused will be recorded for each treatment arm Any change in prophylaxis schedule will be recorded in both treatment arms during the overall study period and will not represent an exclusion criterion from the study
On the other hand some recent data suggest that despite adequate prophylaxis a not negligible percentage of PwH develop arthropathy
Thus an adequate screening of early signs of arthropathy is needed On this hand synovitis is widely considered as one of the parameters to be taken into account for the diagnosis and the surveillance of joint impairment in PwH Synovitis represents a key feature potentially related to under-treatment due to insufficient therapy regimens or to a limited compliance to treatment to pharmacokinetics variability or to demanding dailysport activities Accordingly there is a general agreement on the indication to consider the presence of synovitis as a marker of disease activity in PwH
MATERIALS AND METHODS
Among patients referred to enrolling Haemophilia Centres to be defined consecutive patients with severe FVIII 1 or severe-moderate FVIII 2 haemophilia A without inhibitors will be enrolled according to the above reported inclusion and exclusion criteria For each subject a trained staff will record demographic data including age race ethnicity body mass index BMI kgm2 Information from medical records will also include the number of bleeding episodes and the amount of factor concentrate used during the previous 12 months for regular prophylaxis and for breakthrough bleeding episodes treatment The present study will be organized in 2 phases
Phase 1 US screening All patients will undergo an ultrasound examination of elbows ankles and knees to define joint status and to define presenceabsence of synovitis according to the HEAD-US system Synovitis screening protocol will include examination of the olecranon recess elbow suprapatellar recess knee and anterior recess of the tibiotalar joint ankle For a detailed scanning protocol see Figure 1 Synovitis will be scored as absentminimal score 0 mildmoderate score 1 and severe score 2
Phase 2 Intervention Patients with US evidence of synovitis will be randomly assigned at undergoing a PK assessment with WAPPS-Hemo to start a prophylaxis with any EHL-FVIII targeting a 12 FVIII through level PROPEL-like arm or to continue ongoing standard treatment control arm US examination of the six joints will be repeated monthly for six months and in case of onset of symptoms that might suggest an acute bleeding episode For both treatment arms changes in synovitis status the number of bleeding episodes number of infusions and FVIII consumption will be recorded In case of confirmed hemarthrosis an intensive treatment will be started with the ongoing treatment according to current guidelines During the intensive treatment period the US assessment of the affected joint will be repeated every 7 days The intensive replacement treatment will be stopped when US will demonstrate complete resolution of intra-articular bleeding The time to pain disappearance the time to US evidence of bleeding resolution and the number and doses infused will be recorded for each treatment arm Any change in prophylaxis schedule will be recorded in both treatment arms during the overall study period and will not represent an exclusion criterion from the study
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?:
False
Is an FDA AA801 Violation?:
None