Abstract 4141662: Study of Angiogenic Cell Therapy for Progressive Pulmonary Hypertension: Intervention with Repeat dosing of eNOS-enhanced EPCs: the SAPPHIRE Trial
Bibliographic record
Abstract
In pulmonary arterial hypertension (PAH), widespread pruning of the lung distal arterial bed leads to increased vascular resistance, right heart failure and death. Currently, there are no available therapies designed to revascularize the lung. We assessed the effects of autologous, angiogenic endothelial progenitor cells (EPCs) transfected with endothelial NO synthase (eNOS) in PAH patients receiving available standard-of-care therapies in a 12-month randomized, controlled trial (RCT; NCT03001414). Patients were randomized to receive a course of 4 monthly infusions over the first 6 months consisting of placebo (Arm 1) or eNOS-EPCs (20M cells; Arms 2 and 3) at 0, 1, 2 and 3 months, for a total 80M cells. After 6 months, Arm 1 crossed over to cell infusions, Arm 2 to placebo, whereas Arm 3 received a second course of eNOS-EPCs (total 160M cells). The primary endpoint was change in 6MWD (baseline to 6 months) between patients receiving eNOS-EPCs vs. placebo. However, due to the COVID-19 pandemic the trial was stopped after only 12 of the planned 45 patients were enrolled (5 placebo, 7 cells). While small sample size precluded appropriately powered analyses, a qualitative difference was seen between the eNOS-EPC and placebo groups over the first 6 months (Figure), with a 2-fold greater proportion of patients achieving a 35-meter increase in 6MWD in the cell therapy group (40% vs. 20%, resp). As well, these improvements coincided with cell delivery in all 3 Arms, with a sustained increase in 6MWD over 12 months after a single course of cells in the first 6 months (Arm 2). Treatment with eNOS-EPCs was well tolerated; however, an isolated decrease in 6MWD was apparent 1 month after the first infusion of the second course of cell therapy in Arm 3 patients, with full recovery by the end of the course. This raises the possibility of an immune response to rechallenging patients with this autologous cell product, despite the absence of any clinical indicators, which will be explored by analysis of immune biomarkers. Therefore, the results of the SAPPHIRE trial suggest possible clinical benefit of a single course of 4 infusions of eNOS-EPCs in PAH patients receiving cell therapy and support the performance of a larger RCT.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| 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 | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.007 | 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".