Prevalence of Synovitis in Patients With Haemophilia A (SynoPrev)

Prevalence of Synovitis in Adult Patients With Haemophilia A in Germany and Austria

The aim of this study is to evaluate the prevalence of synovitis in adult patients with haemophilia A.

Study Overview

• Status: Recruiting
• Conditions: Haemophilia A; Synovitis; Hemophilia Arthropathy; Sonography
• Intervention / Treatment: Diagnostic test: Hemophilia Early Arthropathy Detection with Ultrasound (HEAD-US); Haemophilia joint health score (HJHS)

Detailed Description

The bleeding disorder haemophilia causes recurrent spontaneous bleedings primarily into the joints and soft tissues. The reason is a congenital lack of factor VIII (haemophilia A) or factor IX (haemophilia B). In Germany, the most affected joints are the ankle, knee, and elbow. The joint bleedings are accompanied by pain and an inflammatory process that leads to synovitis and ultimately to degenerative joint changes resulting in haemophilic arthropathy: The synovial tissue is responsible for removing blood residuals from the joint cavity. However, blood components, especially iron, induce several changes in the synovial tissue. The resulting synovitis leads to damage of cartilage, bone cysts, osteophytes, and joint effusions. Synovitis can even become a bleeding-independent process, especially after repeated bleeding. According to current knowledge, there is no option to prevent synovitis except for preventing bleedings.

In the aftermath of recurrent joint bleedings, various changes in the synovial tissue, the articular cartilage, and the subchondral bone and blood vessels are observed. These changes are accompanied by restricted joint mobility and musculoskeletal dysfunction. In addition to these peripheral structural changes, various studies show that the entire musculoskeletal system is also affected by recurrent joint bleedings, as it adapts to pain.

Improved therapy over the past decades has led to a reduction in major joint bleeding rates. For this reason, it is important to examine whether this has improved the average joint status and how often patients with haemophilia (PwH) are affected by synovitis at all. Sonography is the radiation-free method of choice for the initial determination of synovitis.

In addition to the structural consequences, joint bleedings also lead to pain and reduction in physical performance. When considering the overall process of degenerative joint changes of PwH, it becomes apparent that this also reduces daily mobility and muscle strength. To the best of our knowledge, the effects of the degree of synovitis on pain perception and physical performance have not been evaluated in previous studies.

For this reason, the prevalence of synovitis in PwH and the consequences in relation to the pain situation and physical performance will be investigated.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Andreas C. Strauss, PD Dr. med.; Phone Number: +4922828714176; Email: andreas.strauss@ukbonn.de

Study Locations

• Germany
  • NRW
    • Bonn, NRW, Germany, 53113
      • Recruiting
      • University Hospital Bonn
      • Contact: Andreas C. Strauss, PD Dr. med.; Phone Number: 004922828714176; Email: andreas.strauss@ukbonn.de
      • Principal Investigator: Andreas C. Strauss, PD Dr. med.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients (≥ 18 years of age) suffering from moderate (FVIII 1-5 %) or severe (FVIII <1 %) haemophilia A.

Description

Inclusion Criteria:

• Participants (≥ 18 years old) suffering from moderate or severe haemophilia A, also with inhibitor or joint replacement
• Complete documentation of hemophilia severity, treatment history (past 12 months), and bleeding events (past 12 months), inhibitor status (at time of enrollment and in past medical history)
• Submitted written consent to participate in the study

Exclusion Criteria:

• Patients suffering from other bleeding disorders conflicting with the research question
• Patients in clinical studies with investigational drugs

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with Haemophilia A; Patients with severe and moderate Haemophilia A (FVIII < 5 %, ≥ 18 years' old)	Diagnostic test: Hemophilia Early Arthropathy Detection with Ultrasound (HEAD-US); Haemophilia joint health score (HJHS); Each subject is examined for the presence of synovitis using the aforementioned diagnostics.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Haemophilia early arthropathy detection with ultrasound (HEAD-US)	HEAD-US protocol examines both elbow, knee and ankle joints sonographically and assesses the presence of synovitis or joint damage from 0-8 points per joint according to Martinoli et al. 2013. A "total score" of 0 to 48 points is achievable. A higher score means a worse joint status.	20 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Hemophilia Joint Health Score version 2.1 (HJHS)	Clinical joint examination according to De la Corte-Rodriguez et al. 2020. HJHS protocol examines both elbow, knee and ankle joints using a goniometer for range of motion and axial alignment (0-3 points), pain numerical rating scale (0-10 points), swelling (0-3 points), crepitation (0-2 points) and gait abnormalities (0-4 points). A "total score" of 0 to 124 points is achievable. A higher score means a worse joint status.	45 minutes
PROMIS-29 Questionaire	Patient-reported outcomes are surveyed using short questionnaires with a stable number of items from seven PROMIS sub scales ("depression", "anxiety", "physical functioning", "impairment due to pain", "fatigue", "sleep impairment", "participation in social roles" and "activities"). The measures use a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the sub scales "participation in social roles and activities" and "physical functioning", a high score is interpreted as a good result and for the sub scales "anxiety", "depression", "fatigue", "impairment due to pain", and "sleep impairment" a low score is a good result.	10 minutes
Haemophilia Activities List (HAL)	to evaluate to subjective physical performance. A higher scores represent a better functional status. Scores can be calculated for each of ten domains of the HAL and a sum score ("Lying / sitting / kneeling / standing" (8-48 Points), "Functions of the legs" (9-54 Points), "Functions of the arms" (4-24 Points), "Use of transportation" (3-18 Points), "Self care" (5-30 Points), "Household tasks" (6-36 Points), "Leisure activities and sports" (7-42 Points), "Upper Extremity Activities" (9-54 Points), "Basic Lower Extremity Activities" (6-36 Points), "Complex Lower Extremity Activities" (9-54 Points), and "Sum score" (42-252 Points).	10 minutes

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline Characteristics	General anamnesis questionnaire (diseases, pain medication, surgeries, haemophilia related clinical data, date of birth, weight in kilograms, hight in centimeters.; Haemophilia treatment past twelve months (on demand/prophylaxis/non-factor therapy/EHL or SHL therapy); Bleeding events past twelve months (traumatic or spontaneous)	15 minutes

Collaborators and Investigators

• Sponsor: University Hospital, Bonn
• Collaborators: Swedish Orphan Biovitrum
• Investigators: Principal Investigator: Andreas C Strauss, PD Dr. med., University Hospital, Bonn

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: March 7, 2024
• First Submitted That Met QC Criteria: April 3, 2024
• First Posted (Actual): April 8, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Prevalence; Synovitis; Haemophilia A
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Blood Coagulation Disorders; Hemophilia A; Synovitis
• Other Study ID Numbers: Elo-Ger-2023-1642

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The publication of anonymous patient data is not allowed by informed consent.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No