P-118. Patient Reported Outcomes (PRO) Analysis of the Phase 2 Multi-Center, Prospective, Randomized, Double-Blind Study Assessing Nitazoxanide for the Treatment of Norovirus in Hematopoietic Stem Cell and Solid Organ Transplant Recipients
Bibliographic record
Abstract
Abstract Background Norovirus (NoV) results in relapsing, remitting diarrhea in immunocompromised hosts (ICH). No prospective studies of existing therapies including nitazoxanide (NTZ) have included evaluation of patient reported outcomes (PRO) or reported impact on patient quality of life (QOL). Methods We conducted a NIH-sponsored multi-center, prospective, randomized, double-blind study of NTZ for the treatment of NoV in adult HSCT and SOT recipients. Subjects with a positive NoV testing and active GI symptoms were randomly assigned (1:1) to NTZ 500 mg twice daily or placebo (P) for 56 consecutives doses and followed for 6 months. PRO diary assessments based on recognized questionnaires were collected: IBSQOL, EuroQOL, PROMIS Emotional, PROMIS GI, PANAS and PROMIS Physical Function Questionnaires.Figure 1.Patient-Reported Quality of Life by EuroQOL-5 Dimension and Study Day – Nitazoxanide vs Placebo, mITT Population Results 31 subjects (16 NTZ, 15 P) were enrolled (Table 1). Early withdrawal was documented in 5 subjects from each group. Thirty (30) had received solid organ transplants. Most had chronic (> = 14d) symptoms (77%). Based on data collected from PRO diaries, there were no significant between-treatment differences for change in diarrhea or nausea from baseline to day 180 (p=0.590 and 0.271). There was no significant difference in median time to 50% reduction in antimotility agents (NTZ 7d vs placebo 5d, p=0.830). However, the EuroQOL-5 questionnaire responses showed that patients seem to report less problems with anxiety/depression (NTZ 29% vs placebo 38%), mobility (21% vs 50%) and usual activities (29 vs 64%) at the end of study drug with NTZ (Fig. 1). There were significant difference in improvement of reported incontinence events between groups over time, which likely impact perceived QOL and activity level. Importantly, analysis of PROs demonstrates the significant and longstanding impact of NoV on ICH with high rates of anxiety/depression and reduced mobility at 180 days. Conclusion PROs from this study provided significant insight into the expected course of NoV infection in ICH, including persistent but intermittent diarrhea, prolonged anxiety and depression, reduced mobility and reduced usual activity even out to 180 days post monitoring. This study provides data to support the use of PROs as primary endpoints in these studies. Disclosures Ajit Limaye, Professor/MD, Memo: Advisor/Consultant|merck: Advisor/Consultant|merck: Grant/Research Support|moderna: Advisor/Consultant|moderna: site investigator|NobelPharma: DSMB member Steven A. Pergam, MD, MPH, Cidara: Advisor/Consultant|F2G: Advisor/Consultant|Global Life Technologies: Grant/Research Support|Symbio: Advisor/Consultant Michael D. Green, MD, MPH, ADMA: Advisor/Consultant|Bristol Myers Squibb: Advisor/Consultant|ITB-MED: Advisor/Consultant|kamada: Honoraria Lara A. Danziger-Isakov, MD, MPH, Aicuris: clinical research contract, paid to institutio|Ansun BioPharma: clinical research contract, paid to institution|Astellas: Advisor/Consultant|Astellas: clinical research contract, paid to institutio|Merck: clinical research contract, paid to institutio|Pfizer: Grant/Research Support|Takeda: clinical research contract, paid to institutio Michael Ison, MD MS, GlaxoSmithKline: Grant/Research Support|UpToDate: Royalties
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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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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".