{"ok":true,"data":{"subject":{"kind":"trial","nctId":"NCT03341156","title":"Administration of Prothrombin Complex Concentrate vs. Standard Transfusion During/After Heart Transplantation","sponsor":"University of Maryland, Baltimore","phases":["PHASE3"],"status":"TERMINATED","indication":null,"disease":"symptomatic heart failure"},"rows":[{"n":1,"question":"Is the biology right?","flags":[{"id":"somatic_driver","label":"Somatic driver evidence","value":"no","detail":"None of F7, PROS1, PROC, VEGFA, INSR has somatic-mutation evidence in symptomatic heart failure","rule":"Open Targets has somatic-mutation evidence for the target in this cancer","source":{"label":"Open Targets: F7 in symptomatic heart failure","url":"https://platform.opentargets.org/evidence/ENSG00000057593/MONDO_0005254","date":"2026-11-12T04:43:39.575Z"},"context":[]},{"id":"human_genetic","label":"Human genetic evidence","value":"no","detail":"No germline or somatic evidence for F7, PROS1, PROC, VEGFA, INSR in symptomatic heart failure","rule":"Any germline or somatic human genetic evidence for the target in this cancer, counted apart from animal-model and literature evidence","source":{"label":"Open Targets: F7 in symptomatic heart failure","url":"https://platform.opentargets.org/evidence/ENSG00000057593/MONDO_0005254","date":"2026-11-12T04:43:39.575Z"},"context":[]},{"id":"pediatric_target","label":"Pediatric target","value":"no","detail":"Not on the FDA list","rule":"Target is on FDA's Pediatric Molecular Target List (relevant targets); membership alone neither requires nor waives a study","source":{"label":"FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01))","url":"https://www.fda.gov/media/191157/download?attachment","date":"2026-11-11T07:05:03Z"},"context":[]},{"id":"haematologic","label":"Haematologic cancer","value":"no","detail":"Solid tumour","rule":"From the indication, or the registry conditions when no indication matches","source":{"label":"ClinicalTrials.gov NCT03341156","url":"https://clinicaltrials.gov/study/NCT03341156","date":"2026-11-12T04:43:39.575Z"},"context":[{"figure":"Likelihood of approval from phase 1: 7.5% haematologic vs 4.6% solid","dataset":"BIO / Informa / QLS 2021","years":"2011–2020","caveat":"Population-level, not a prediction."}]}],"facts":[{"label":"F7 (via Kcentra)","text":"Open Targets has no association between F7 and symptomatic heart failure.","source":{"label":"Open Targets: F7 in symptomatic heart failure","url":"https://platform.opentargets.org/evidence/ENSG00000057593/MONDO_0005254","date":"2026-11-12T04:43:39.575Z"}},{"label":"PROS1 (via Kcentra)","text":"Open Targets has no association between PROS1 and symptomatic heart failure.","source":{"label":"Open Targets: PROS1 in symptomatic heart failure","url":"https://platform.opentargets.org/evidence/ENSG00000184500/MONDO_0005254","date":"2026-11-12T04:43:39.575Z"}},{"label":"PROC (via Kcentra)","text":"Open Targets has no association between PROC and symptomatic heart failure.","source":{"label":"Open Targets: PROC in symptomatic heart failure","url":"https://platform.opentargets.org/evidence/ENSG00000115718/MONDO_0005254","date":"2026-11-12T04:43:39.575Z"}},{"label":"VEGFA (via Frozen Plasma Product)","text":"Open Targets has no association between VEGFA and symptomatic heart failure.","source":{"label":"Open Targets: VEGFA in symptomatic heart failure","url":"https://platform.opentargets.org/evidence/ENSG00000112715/MONDO_0005254","date":"2026-11-12T04:43:39.575Z"}},{"label":"INSR (via Human)","text":"Open Targets has no association between INSR and symptomatic heart failure.","source":{"label":"Open Targets: INSR in symptomatic heart failure","url":"https://platform.opentargets.org/evidence/ENSG00000171105/MONDO_0005254","date":"2026-11-12T04:43:39.575Z"}}],"pending":[{"what":"Normal-tissue expression in vital organs","source":"Human Protein Atlas (ticket 36)"},{"what":"Pan-essential in cell lines","source":"DepMap (ticket 36)"},{"what":"Approved drug on this target","source":"Drugs@FDA (ticket 30)"}]},{"n":2,"question":"Can the result be trusted?","flags":[{"id":"randomised","label":"Randomised","value":"yes","detail":"Randomised allocation","rule":"Registry allocation field","source":{"label":"ClinicalTrials.gov NCT03341156","url":"https://clinicaltrials.gov/study/NCT03341156","date":"2026-11-12T04:43:39.575Z"},"context":[]},{"id":"small_denominator","label":"Small denominator","value":"yes","detail":"14 enrolled; each patient moves a rate by 100 ÷ 14 = 7.1 points","rule":"Enrolment under 30; the arithmetic is shown, not a benchmark","source":{"label":"ClinicalTrials.gov NCT03341156","url":"https://clinicaltrials.gov/study/NCT03341156","date":"2026-11-12T04:43:39.575Z"},"context":[]},{"id":"primary_os","label":"Primary endpoint is overall survival","value":"no","detail":"Amount of Chest Tube Drainage","rule":"A registered primary outcome measure names overall survival","source":{"label":"ClinicalTrials.gov NCT03341156","url":"https://clinicaltrials.gov/study/NCT03341156","date":"2026-11-12T04:43:39.575Z"},"context":[{"figure":"Non-OS primary endpoint: odds ratio 2.79 for a positive phase 3","dataset":"Otsuka 2021, 400 phase 3 oncology trials","years":"to 2020","caveat":"Shown with the next figure: a surrogate is easier to hit, and often a weak guide to survival."},{"figure":"52% of surrogate-to-OS correlations are low","dataset":"Prasad 2015","years":"published to 2014","caveat":"Shown with the figure above."}]},{"id":"results_overdue","label":"Results overdue","value":"no","detail":"Results posted 2026-11-10","rule":"Primary completion (actual) more than 12 months ago and no results posted to the registry","source":{"label":"ClinicalTrials.gov NCT03341156","url":"https://clinicaltrials.gov/study/NCT03341156?tab=results","date":"2026-11-12T04:43:39.575Z"},"context":[]}],"facts":[],"pending":[{"what":"Treated and evaluable counts, assessor, confirmed response, follow-up and data cutoff","source":"Readout extraction (ticket 32)"},{"what":"Primary endpoint changed between registry versions","source":"Registry versions in the store (ticket 32)"}]},{"n":3,"question":"What must it beat?","flags":[],"facts":[],"pending":[{"what":"Control-arm result and approved therapies for the same segment, with label links","source":"Drugs@FDA, FDA labels and readouts (tickets 30, 32)"}]},{"n":4,"question":"Too crowded, or too late?","flags":[],"facts":[{"label":"Stopped on this target","text":"39 terminated, withdrawn or suspended trials of drugs against F7; 7 give no reason. Reasons are quoted as the registry gives them on the target page.","source":{"label":"F7: what already stopped","url":"/target/ENSG00000057593#stopped","date":"2026-11-12T04:43:39.587Z"}}],"pending":[{"what":"Programs on the target by phase and months behind the leader","source":"Programs and Drugs@FDA (ticket 33)"}]},{"n":5,"question":"Can it be approved, and stay approved?","flags":[{"id":"single_country","label":"Single-country","value":"yes","detail":"All 3 sites in United States","rule":"All listed sites are in one country; the share of US sites is shown","source":{"label":"ClinicalTrials.gov NCT03341156","url":"https://clinicaltrials.gov/study/NCT03341156?tab=locations","date":"2026-11-12T04:43:39.575Z"},"context":[]},{"id":"eu_pip","label":"EU paediatric investigation plan","value":"yes","detail":"EMEA-003523-PIP01-23 (Interleukin-2/Interleukin-1 beta, human/Granulocyte colony-stimulating factor/Tumour necrosis factoralpha/ Interferon gamma, Treatment of head and neck epithelial malignant neoplasms): W: decision granting a waiver in all age groups for all conditions or indications, 8 Mar 2024; EMEA-001312-PIP02-19 (alpha1-proteinase inhibitor (human), Prevention of graft versus host disease): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 15 Apr 2020; EMEA-001312-PIP03-19 (alpha1-proteinase inhibitor (human), Treatment of acute graft-versus-host disease (aGvHD)): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 1 Dec 2020; EMEA-002888-PIP01-20 (alpha1-proteinase inhibitor (human), Treatment of emphysema secondary to alpha 1-proteinase inhibitor deficiency): W: decision granting a waiver in all age groups for all conditions or indications, 27 Jan 2021; +2 more","rule":"An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name","source":{"label":"EMA data download (dated snapshot)","url":"https://www.ema.europa.eu/en/documents/report/medicines-output-paediatric_investigation_plans-output-json-report_en.json","date":"2026-11-11T09:12:26Z"},"context":[]},{"id":"eu_orphan","label":"EU orphan designation","value":"yes","detail":"EU/3/18/2114 withdrawn 14 Dec 2018: Treatment in solid organ transplantation; EU/3/24/2983 positive 10 Nov 2024: Treatment of cutaneous T-cell lymphoma; EU/3/16/1648 withdrawn 28 Apr 2016: Treatment of soft tissue sarcoma; EU/3/06/405 positive 23 Oct 2006: Treatment of renal-cell carcinoma","rule":"An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status","source":{"label":"EMA data download (dated snapshot)","url":"https://www.ema.europa.eu/en/documents/report/medicines-output-orphan_designations-json-report_en.json","date":"2026-11-11T09:12:26Z"},"context":[]},{"id":"eu_authorised","label":"Authorised in the EU","value":"yes","detail":"Cinryze: authorised since 15 Jun 2011; Respreeza: authorised since 20 Aug 2015","rule":"An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file","source":{"label":"EMA data download (dated snapshot)","url":"https://www.ema.europa.eu/en/documents/report/medicines-output-medicines_json-report_en.json","date":"2026-11-11T09:12:26Z"},"context":[]},{"id":"fda_orphan","label":"FDA orphan designation","value":"not published","detail":"FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the link","rule":"Would be: an FDA orphan designation names the drug","source":{"label":"FDA orphan designations search","url":"https://www.accessdata.fda.gov/scripts/opdlisting/oopd/","date":""},"context":[]},{"id":"fda_ped_approval","label":"FDA pediatric oncology approval","value":"no","detail":"FDA's table lists no pediatric approval of Kcentra, Frozen Plasma Product, Human","rule":"FDA's Pediatric Oncology Drug Approvals table names the drug","source":{"label":"FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03)","url":"https://www.fda.gov/about-fda/oncology-center-excellence/pediatric-oncology-drug-approvals","date":"2026-11-12T04:43:39.601Z"},"context":[]},{"id":"studies_under_18","label":"Registered studies open to children","value":"yes","detail":"3385 interventional studies of Kcentra, Frozen Plasma Product, Human include patients under 18; 665 are recruiting, not yet recruiting or active","rule":"The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age","source":{"label":"ClinicalTrials.gov search","url":"https://clinicaltrials.gov/search?intr=%22Kcentra%22+OR+%22Frozen+Plasma+Product%22+OR+%22Human%22&aggFilters=ages%3Achild%2CstudyType%3Aint","date":"2026-11-12T04:43:39.601Z"},"context":[]}],"facts":[{"label":"Caveat","text":"Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where the sites are is a fact about the record, not a judgement of its quality."},{"label":"Rare pediatric disease voucher","text":"FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news.","source":{"label":"FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs","url":"https://www.fda.gov/industry/medical-products-rare-diseases-and-conditions/rare-pediatric-disease-designation-and-priority-review-voucher-programs","date":"2026-11-11"}}],"pending":[{"what":"Precedent approvals for target, modality and endpoint; accelerated-approval status","source":"Drugs@FDA and FDA accelerated-approval tables (ticket 30)"}]},{"n":6,"question":"Can the sponsor finish?","flags":[],"facts":[{"label":"Sponsor","text":"University of Maryland, Baltimore (academic or other)","source":{"label":"ClinicalTrials.gov NCT03341156","url":"https://clinicaltrials.gov/study/NCT03341156","date":"2026-11-12T04:43:39.575Z"}},{"label":"principal investigator","text":"Kenichi Tanaka, MD, University of Maryland, Baltimore","source":{"label":"Person page","url":"/person/Kenichi%20Tanaka%2C%20MD","date":"2026-11-12T04:43:39.575Z"}},{"label":"principal investigator","text":"Kathirvel Surbramaniam, MD, University of Pittsburgh Medical Center","source":{"label":"Person page","url":"/person/Kathirvel%20Surbramaniam%2C%20MD","date":"2026-11-12T04:43:39.575Z"}}],"pending":[{"what":"Filed cash, quarterly spend and the runway arithmetic","source":"SEC XBRL company facts (ticket 37)"},{"what":"Sponsor's completed vs stopped oncology trials and results-reporting record","source":"Registry, by company (ticket 37)"}]}],"limits":"Public records cannot show: sales forecasts; a probability of success for this asset; full deal terms and net prices; FDA designations and action dates before approval (shown only as company-reported); clinical holds unless the company disclosed them; manufacturing; patents on unapproved drugs; whether preclinical findings have been replicated.","sources":[{"label":"ClinicalTrials.gov NCT03341156","url":"https://clinicaltrials.gov/study/NCT03341156","date":"2026-11-12T04:43:39.575Z"},{"label":"Open Targets Platform","url":"https://platform.opentargets.org","date":"2026-11-12T04:43:39.575Z"},{"label":"FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01))","url":"https://www.fda.gov/media/191157/download?attachment","date":"2026-11-11T07:05:03Z"}]},"source":"ClinicalTrials.gov + Open Targets","fetchedAt":"2026-11-12T04:43:39.574Z"}