Trial reportClinical and translational science2019
PF-04447943, a Phosphodiesterase 9A Inhibitor, in Stable Sickle Cell Disease Patients: A Phase Ib Randomized, Placebo-Controlled Study.
Trial report in Clinical and translational science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Hydroxyurea (hydroxycarbamide) for sickle cell disease.The Cochrane database of systematic reviews · 2022Pooled it
- Hederagenin Attenuates Cardiac Remodeling by Targeting Phosphodiesterase 9A.Phytotherapy research : PTR · 2026Article
- Selective AMPKβ1 activation induces fetal hemoglobin in human erythroid cells and sickle cell mice via the noncanonical NRF2 pathway.Science advances · 2025Article
- TRIM32 promotes tumor immune evasion and impedes Anti-PD-1 treatment by inducing immunosuppressive macrophages in gastric cancer.Journal of translational medicine · 2025Article
- Review
- Phosphodiesterase Inhibition to Sensitize Non-Small-Cell Lung Cancer to Pemetrexed: A Double-Edged Strategy.Cancers · 2024Article
- Drug Discovery and Development Targeting Dementia.Pharmaceuticals (Basel, Switzerland) · 2023Review
- BAY-7081: A Potent, Selective, and Orally Bioavailable Cyanopyridone-Based PDE9A Inhibitor.Journal of medicinal chemistry · 2022Article
- Inhibition of Colon Cancer Cell Growth by Phosphodiesterase Inhibitors Is Independent of cGMP Signaling.The Journal of pharmacology and experimental therapeutics · 2022Article
- Increased Energy Expenditure and Protection From Diet-Induced Obesity in Mice Lacking the cGMP-Specific Phosphodiesterase PDE9.Diabetes · 2021Article
- Research progress of phosphodiesterase inhibitors in inflammatory bowel disease treatment.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2021Review
- Sickle cell vaso-occlusion: The dialectic between red cells and white cells.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Computational Study on Selective PDE9 Inhibitors on PDE9-Mg/Mg, PDE9-Zn/Mg, and PDE9-Zn/Zn Systems.Biomolecules · 2021Article
- Nitric oxide and sickle cell disease-Is there a painful connection?Experimental biology and medicine (Maywood, N.J.) · 2021Review
- PDE9 Inhibitor PF-04447943 Attenuates DSS-Induced Colitis by Suppressing Oxidative Stress, Inflammation, and Regulating T-Cell Polarization.Frontiers in pharmacology · 2021Article
- CRD-733, a Novel PDE9 (Phosphodiesterase 9) Inhibitor, Reverses Pressure Overload-Induced Heart Failure.Circulation. Heart failure · 2021Article
- Fetal hemoglobin in sickle cell anemia.Blood · 2020Review
- cGMP: a unique 2nd messenger molecule - recent developments in cGMP research and development.Naunyn-Schmiedeberg's archives of pharmacology · 2020Review
- The Evolving Pharmacotherapeutic Landscape for the Treatment of Sickle Cell Disease.Mediterranean journal of hematology and infectious diseases · 2020Review
- Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond.Nature reviews. Drug discovery · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This phase Ib study randomized patients with stable sickle cell disease (SCD) aged 18-65 years to twice-daily PF-04447943 (a phosphodiesterase 9A inhibitor; 5 or 25 mg) or placebo, with/without hydroxyurea coadministration, for up to 29 days. Blood samples were collected at baseline and various posttreatment time points for assessments of PF-04447943 pharmacokinetics (PKs)/pharmacodynamics (PDs). Change from baseline in potential SCD-related biomarkers was evaluated. Of 30 patients, 15 received hydroxyurea and 28 completed the study. PF-04447943, with/without hydroxyurea, was generally well tolerated, with no treatment-related serious adverse events. Plasma PF-04447943 exposure was dose proportional. Twice-daily PF-04447943 25 mg significantly reduced the number and size of circulating monocyte-platelet and neutrophil-platelet aggregates and levels of circulating soluble E-selectin at day 29 vs. baseline (adjusted P < 0.15). PF-04447943 demonstrated PK/PD effects suggestive of inhibiting pathways that may contribute to vaso-occlusion. This study also provides guidance regarding biomarkers for future SCD studies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.