S390 Efficacy and Safety of On-Demand Vonoprazan versus Placebo in the Treatment of Heartburn in Symptomatic Nonerosive Reflux Disease (NERD) Patients: A Phase 2 Randomized Controlled Trial
Notice bibliographique
Résumé
Introduction: Current treatment for NERD is daily acid-suppressive therapy; however, on-demand treatment is an attractive option for long-term management. Vonoprazan, a potassium-competitive acid blocker, rapidly and profoundly suppresses gastric acid. The aim of this study was to evaluate the efficacy and safety of vonoprazan vs placebo for on-demand treatment of symptomatic NERD. Methods: This Phase 2, double-blind, placebo-controlled study (NCT04799158) enrolled NERD patients (normal endoscopy, heartburn episodes for ≥6 months, heartburn on ≥4/7 consecutive days) into a 4-week run-in period of once-daily vonoprazan 20mg. Patients without heartburn in the last 7 days of the run-in period were randomized 1:1:1:1 to receive vonoprazan 10mg, 20mg, 40mg, or placebo on-demand for 6 weeks. Patients were asked to take no more than one dose of study drug for 24h after a heartburn episode and to take no rescue antacids ≤3h after taking study drug. Patients recorded heartburn symptoms, drug and antacid use in an electronic diary. The primary endpoint was the % of evaluable heartburn episodes with complete and sustained relief (within 3h and with no further heartburn reported for 24h after taking study drug) during the on-demand treatment period. The onset of complete and sustained relief was evaluated within 30min and 1, 1.5, 2, and 3h after study drug. Results: Of 458 patients entering the run-in period, 207 (females: 125; mean age: 54y) were eligible and randomized to treatment. For the primary endpoint, in the vonoprazan 10, 20, and 40mg groups, 56.0% (201/359), 60.6% (198/327) and 70.0% (226/323) of heartburn episodes met the criteria for complete and sustained relief, respectively, vs 27.3% (101/370) for placebo (P< 0.0001 for each vonoprazan treatment vs placebo) (Table). Significant differences in complete and sustained relief occurred as early as 1h after study drug for all vonoprazan doses. In the on-demand period, 21.3% of patients receiving placebo reported a treatment-emergent adverse event (TEAE) vs 16.3%, 18.4%, and 16.7% of those on vonoprazan 10, 20, and 40mg, respectively. No TEAE was reported by >1 patient per group. No serious TEAEs were reported. Conclusion: The results suggest that on-demand vonoprazan treatment for the relief of episodic heartburn in NERD patients is efficacious and well-tolerated. On-demand vonoprazan treatment may offer NERD patients an attractive alternative to daily heartburn therapy. Table 1. - Comparison of efficacy endpoint results between the different vonoprazan doses and placebo Endpoint Vonoprazan10 mg n=52 Vonoprazan20 mg n=52 Vonoprazan40 mg n=51 Placebo n=52 Heartburn episodes with complete and sustained relief within 3 hoursa n/N evaluable episodesb (%) 201/359 (56.0) 198/327 (60.6) 226/323 (70.0) 101/370 (27.3) P-value (vs placebo) < 0.0001 < 0.0001 < 0.0001 - Timing of complete and sustained reliefa, n/N evaluable episodesb (%) Within 30 minutes 31/359 (8.6) 17/327 (5.2) 9/323 (2.8) 21/370 (5.7) P-value (vs placebo) 0.15 0.87 0.09 - Within 1 hour 101/359 (28.1) 63/327 (19.3) 74/323 (22.9) 44/370 (11.9) P-value (vs placebo) < 0.0001 0.0083 0.0002 - Within 1.5 hours 151/359 (42.1) 103/327 (31.5) 139/323 (43.0) 67/370 (18.1) P-value (vs placebo) < 0.0001 < 0.0001 < 0.0001 - Within 2 hours 182/359 (50.7) 151/327 (46.2) 187/323 (57.9) 81/370 (21.9) P-value (vs placebo) < 0.0001 < 0.0001 < 0.0001 - (a)Complete and sustained relief is defined as complete relief with no antacid taken within the indicated time frame after taking study drug and no further heartburn reported for 24 hours after taking study drug.(b)An evaluable heartburn episode is defined as any for which study drug was taken and for which the subject completed ≥1 entry in the heartburn episode diary.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,004 | 0,002 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,004 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,018 | 0,002 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».