Effect of a Novel Macrophage-Regulating Drug on Wound Healing in Patients With Diabetic Foot Ulcers: A Randomized Clinical Trial.

Importance: Delayed healing of diabetic foot ulcers (DFUs) is known to be caused by dysregulated M1/M2-type macrophages, and restoring the balance between these macrophage types plays a critical role in healing. However, drugs used to regulate M1/M2 macrophages have not yet been studied in large randomized clinical trials. Objective: To compare the topical application of ON101 cream with use of an absorbent dressing (Hydrofiber; ConvaTec Ltd) when treating DFUs. Design, Setting, and Participants: This multicenter, evaluator-blinded, phase 3 randomized clinical trial was performed in 21 clinical and medical centers across the US, China, and Taiwan from November 23, 2012, to May 11, 2020. Eligible patients with debrided DFUs of 1 to 25 cm2 present for at least 4 weeks and with Wagner grade 1 or 2 were randomized 1:1 to receive ON101 or control absorbent dressings. Interventions: Twice-daily applications of ON101 or a absorbent dressing changed once daily or 2 to 3 times a week for 16 weeks, with a 12-week follow-up. Main Outcomes and Measures: The primary outcome was the incidence of complete healing, defined as complete re-epithelialization at 2 consecutive visits during the treatment period assessed on the full-analysis set (FAS) of all participants with postrandomization data collected. Safety outcomes included assessment of the incidences of adverse events, clinical laboratory values, and vital signs. Results: In the FAS, 236 eligible patients (175 men [74.2%]; mean [SD] age, 57.0 [10.9] years; mean [SD] glycated hemoglobin level, 8.1% [1.6%]) with DFUs classified as Wagner grade 1 or 2 (mean [SD] ulcer area, 4.8 [4.4] cm2) were randomized to receive either the ON101 cream (n = 122) or the absorbent dressing (n = 114) for as long as 16 weeks. The incidence of complete healing in the FAS included 74 patients (60.7%) in the ON101 group and 40 (35.1%) in the comparator group during the 16-week treatment period (difference, 25.6 percentage points; odds ratio, 2.84; 95% CI, 1.66-4.84; P < .001). A total of 7 (5.7%) treatment-emergent adverse events occurred in the ON101 group vs 5 (4.4%) in the comparator group. No treatment-related serious adverse events occurred in the ON101 group vs 1 (0.9%) in the comparator group. Conclusions and Relevance: In this multicenter randomized clinical trial, ON101 exhibited better healing efficacy than absorbent dressing alone in the treatment of DFUs and showed consistent efficacy among all patients, including those with DFU-related risk factors (glycated hemoglobin level, ≥9%; ulcer area, >5 cm2; and DFU duration, ≥6 months). Trial Registration: ClinicalTrials.gov Identifier: NCT01898923.

Data feedback reduces door-to-balloon time in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Current guidelines recommend a goal of door-to-balloon (D2B) time < 90 min for patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). We aim to prospectively determine the effect of data feedback on D2B time and its seven individual components in primary PCI. From December 7, 2007, to June 2, 2009, 116 consecutive patients with STEMI who received PCI within 12 h of symptom onset were enrolled, including 56 patients before and 60 patients after the implementation of data feedback on July 28, 2008. The proportion of patients treated within 90 min increased from 26.8 to 55.0% (p = 0.002). On multivariable analyses, data feedback (OR 5.3, p = 0.003), known coronary artery disease (OR 5.6, p = 0.043), regular hours presentation (OR 3.3, p = 0.048), and arrival by transfer (OR 14.0, p = 0.003) were independent predictors of a D2B time less than 90 min. Median D2B time decreased from 112 min before data feedback to 87 min after data feedback (p < 0.001). The most significant decrease occurred in median door-to-ECG (11 vs. 3 min, p < 0.001), consult-to-cardiologist (5 vs. 3 min, p < 0.001), and puncture-to-balloon (21 vs. 17 min, p = 0.004) time. Data feedback to the emergency department and catheterization laboratory staff decreases D2B time in primary PCI. This simple approach may be the best first step to decrease D2B time in hospitals that are still striving to achieve the goal of D2B time < 90 min.