Results from a Prospective, Dose Escalating, Prophylaxis Study in Young Boys with Severe Hemophilia a in China: The China Hemophilia Individualized Prophylaxis Study (CHIPS) (NCT02999308)
Bibliographic record
Abstract
Abstract Background: In China, 90% of boys with severe hemophilia A (SHA) manifest significant arthropathy by age 6 years (Wu R et al Haemophilia, 2014). Short‐term pilot studies demonstrated that low‐dose prophylaxis (10‐15 IU/kg x2 /week) reduced joint bleeds by 80% but was ineffective in eliminating joint damage (Wu R et al Haemophilia, 2011, Tang L et al Haemophilia, 2013). Optimizing prophylaxis in China for boys with SHA is an urgent priority. Aims: To investigate the efficacy of an individualized, dose escalating prophylaxis protocol in young boys with SHA in China Methods: This is a prospective, ethics approved clinical trial conducted at 2 major Hemophilia Treatment centers in China. Boys with SHA (baseline FVIII 50 Exposure Days and a history of index joint (elbows, knees, ankles) bleeds were eligible. The design included 4 dose escalation steps; Step 1: 10‐15 IU/kg x2/week; Step 2: 10‐15 IU/Kg, x3/week; Step 3: 15‐20 IU/Kg x3/week; and Step 4: 20‐25 IU/Kg every other day. A priori escalation criteria were based on the frequency of index joint bleeds, scores from the Hemophilia Joint Health Score (HJHS) and Ultrasound (US) examinations of index joints. Results: 30 patients were consented and enrolled, with only 1 drop-out. The mean age was 4.8 yrs. (range: 2.1 ‐ 7.9 yrs.) and the median follow up observation period was 10 months (range: 6 ‐11 months). In total, the patients have completed 76% of the required number of months on study (275/360 patient months). Musculoskeletal (MSK) assessment showed a total of 19 boys with target joints (65%). In addition, a total of 22 patients completed 36 dose escalations. Of these patients currently on prophylaxis, 8 patients are on step 1 (28%); 9 on step 2 (31%), 10 on step 3 (34%); and 2 on step 4 (7%). The criterion for escalations are summarized in Table 2. Conclusions: This is the first prospective, individualized, dose escalating prophylaxis study for boys with SHA in China with the goal of minimizing bleeding and joint damage. Findings from the HJHS and US examinations to guide dose escalation, in conjunction with index joint bleeds, is a unique feature of this clinical trial. Our results indicate a promising reduction in joint bleeds by using the 4-step escalation low dose regimens with equal utilization of Steps 1, 2 and 3 by the patients. Low dose prophylaxis may be ineffective in some cases and assessments of bleeding patterns and joint structure/function is important to inform modification of prophylactic regimens. These observations will be useful in the design of cost effective prophylaxis regimens for boys with SHA in China. This study is financially supported by a grant from Bayer HealthCare Co. Ltd., China. Download : Download high-res image (222KB) Download : Download full-size image Disclosures Wu: Bayer Healthcare Co. Ltd., China: Employment.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".