Tadalafil treatment for fetuses with early-onset growth restriction: a protocol for a multicentre, randomised, placebo-controlled, double-blind phase II trial (TADAFER IIb)
Shintaro MakiHiroaki TanakaSho TakakuraMasafumi NiiKayo TanakaToru OguraMayumi KoteraYuki NishimuraSatoshi TamaruTakafumi UshidaYasuhiro TanakaNorihiko KikuchiTadatsugu KinjoHiroshi KawamuraMayumi TakanoK. NakamuraSachie SugaMichi KasaiOsamu YasuiKenji NagaoYuka MaegawaTomomi KotaniMasayuki EndoIchiro YasuhiShigeru AokiYoichi AokiYoshio YoshidaMasahiko NakataAkihiko SekizawaTomoaki Ikeda
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Abstract:
TheTADAlafil treatment for Fetuses with early-onset growth Restriction: multicentrer, randomizsed, phase II trial (TADAFER II) study showed the possibility of prolonging the pregnancy period in cases of early-onset fetal growth restriction; however, it was an open-label study. To establish further evidence for the efficacy of tadalafil in this setting, we planned a multicentre, randomised, placebo-controlled, double-blind trial.This trial will be conducted in 180 fetuses with fetal growth restriction enrolled from medical centres in Japan; their mothers will be randomised into three groups: arm A, receiving two times per day placebo; arm B, receiving one time per day 20 mg tadalafil and one time per day placebo and arm C, receiving 20 mg two times per day tadalafil. The primary endpoint is the prolongation of gestational age at birth, defined as days from the first day of the protocol-defined treatment to birth. To minimise bias in terms of fetal baseline conditions and timing of delivery, a fetal indication for delivery as in TADAFER II will be established in this trial. The investigator will evaluate fetal baseline conditions at enrolment and decide the timing of delivery based on this indication.This study has been approved by Mie University Hospital Clinical Research Review Board on 22 July 2019 (S2018-007). Written informed consent will be obtained from all mothers before recruitment. Our findings will be widely disseminated through peer-reviewed publications.jRCTs041190065.Keywords:
Clinical endpoint
Intrauterine growth restriction
Phosphodiesterase inhibitor
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The data are related to the proteomic analysis of 43 newborns with intrauterine growth retardation (IUGR) and 45 newborns with appropriate weight for gestational age (AGA) carried out by separation via 2DE and analyzed by MS-TOF/TOF. All newborns were separated into three gestational age groups, "Very Preterm" 29-32 weeks, "Moderate Preterm" 33-36 weeks, and, "Term" ≥37weeks. From each newborn, blood was drawn three times from birth to 1 month life. High-abundant serum proteins were depleted, and the minority ones were separated by 2DE and analyzed for significant expression differences. The data reflect analytic and clinic variables analyzed globally and categorized by gestational age in relation to IUGR and the optimization of conditions for 2-DE separation. The data from this study are related to the research article entitled "Alterations of Protein Expression in Serum of Infants with Intrauterine Growth Restriction and Different Gestational Ages" (M.D. Ruis-González, M.D. Cañete, J.L. Gómez-Chaparro, N. Abril, R. Cañete, J. López-Barea, 2015) [1]. The present dataset of serum IUGR newborn proteome can be used as a reference for any study involving intrauterine growth restriction during the first month of life.
Intrauterine growth restriction
Proteome
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Read the full review for this Faculty Opinions recommended article: Adherence to initial PDE-5 inhibitor treatment: randomized open-label study comparing tadalafil once a day, tadalafil on demand, and sildenafil on demand in patients with erectile dysfunction.
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Open label
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On demand
Open label
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A new type of phosphodiesterase 5 inhibitor, Tadalafil, has been used clinically to treat erectile dysfunction (ED). In this review, we analyzed the recent findings from the clinical trials on tadalafil in ED treatment. All data showed that oral tadalafil was an effective and well-tolerated therapeutic for ED, with many potential pharmacological actions. All this may help to give full play to the clinical value of tadalafil.
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Objective To assess the cause of tadalafil failure and the feasibility of successfully rechallenging nonresponding patients. Methods A total of 80 consecutive erectile dysfunction ( ED ) patients who claimed poor response to tadalafil were enrolled into the study.A self-administered tadalafil-use questionnaire composed of eight questions was applied to assess how they had used tadalafil.Subjects were given thorough instruction based on individual answers and four doses of tadalafil 20mg.After a 2-week follow-up,end point efficacy of rechallenge was evaluated using the sexual encounter profile (SEP),which was recommended by international advisory panel in 2004. Results A total of 45 subjects had one or more areas of major suboptimal use of tadalafil:21.2％ did not know that sexual stimulation was necessary for tadalafil to work,87.5％ attempted to use tadalafil less than four times,57.5％ took a maximal dose less than 20 mg,and 84％ felt nervous or anxious.Of the 65 patients undergoing tadalafil rechallenge,30 patients answered “yes” to SEP2 and SEP3.The response rate to rechallenge was 46.2％ ( 30/65 ). Conclusions Inappropriate use of tadalafil was major cause of tadalafil non-pesponse.The efficacy of tadalafil could be improved to a better extent by education of patients.
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Tadalafil; Medical futility; Salvage therapy
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On demand
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Background: Tadalafil, a long-acting phosphodiesterase-5 inhibitor (PDE-5) is the most recent oral agent to receive FDA approval for the treatment of pulmonary arterial hypertension (PAH). Objective: With several new agents emerging for the treatment of PAH, this article reviews tadalafil, the compound and its properties, clinical evidence supporting its use, and the role of tadalafil in the current treatment approach for patients with PAH. Methods: A broad PubMed literature search was performed to identify the most current data on the use of tadalafil for PAH. Results: Tadalafil received FDA approval in 2009 following the recently published pivotal trial that demonstrated that the use of tadalafil 40 mg once daily was well tolerated, improved exercise capacity and quality of life measures and reduced time to clinical worsening in PAH patients. As the second PDE-5 inhibitor to gain approval for PAH, clinical properties such as its long half-life leading to once-daily dosing and possibly improved compliance, as well as potential cost benefit, may distinguish tadalafil from sildenafil in the widespread treatment of PAH.
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Intrauterine growth restriction
Association (psychology)
Growth restriction
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