QUantum Genomics Incremental Dosing in Heart Failure - QUID-HF (QUID-HF)
2018年10月11日 更新者：Quantum Genomics SA
A Randomized, Double-blind, Multi-centre Study to Assess Safety and Efficacy of Incremental Doses of QGC001 in Patients With NYHA Class II/III Chronic Heart Failure (HF) With Left Ventricular Systolic Dysfunction Versus Placebo.
Heart Failure (HF) a common clinical condition characterized by either by a heart that does not pump sufficiently or becomes stiff. A variety of mechanisms contribute to progressive cardiac remodeling and dysfunction.
A new therapeutic approaches by preventing activation of the brain neuromodulatory pathway, may lead to improve HF.
QCG001 is a prodrug of EC33, a aminopeptidase A (APA) inhibitor. QCG001 has been shown to be an antihypertensive agent in animal models.
This study investigates the safety and efficacy of QGC001 in HF patients.
調査の概要
詳細な説明
Despite advances in care, prognosis remains poor once overt Heart Failure (HF) has developed. HF is a common clinical condition characterized by either by a heart that does not pump sufficiently or becomes stiff and it is associates with higher incidences of patient illness and death in both case. A variety of mechanisms contribute to progressive cardiac remodeling and dysfunction.
A new therapeutic approaches by preventing activation of the brain neuromodulatory pathway, may lead to improve HF.
QCG001 is a prodrug of EC33, a specific and selective of the aminopeptidase A (APA) inhibitor. QCG001 has been shown to be an antihypertensive agent in animal models.
This study investigates the safety and efficacy of QGC001 up-titrated form 50mg twice daily to a maximum of 500 mg twice daily, on patients with worsening chronic HF during 28 days and 7 days after discontinuation (day 35).
6 European countries are involved in this study (France, Netherlands, Germany, Norway, Poland and United Kingdom) including 20 investigational hospitals. Patients would be followed during 35 days and inclusion period lasts until December 2017.
研究の種類
介入
入学 (実際)
23
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Dundee、イギリス、DD1 9SY
- Ninewells Hospital
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England
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Birmingham、England、イギリス、B18 7QH
- University of Birmingham Institute of Cardiovascular Sciences City Hospital,
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Groningen、オランダ、9713GZ
- University Medical Center Groningen
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Maastricht、オランダ、PO 5800
- Maastricht University Medical Centre
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Frýdek-Místek、チェコ、73801
- Hospital of Fridek-Mistek P.O.
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Praha、チェコ、12808
- General University Hospital
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Berlin、ドイツ
- Charity Universitatsmedizin Berlin
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Hannover、ドイツ、D-30625
- Medizinische Hochschule Hannover
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Homburg、ドイツ、66421
- Klinik für Innere Medizin III
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Stavanger、ノルウェー、4011
- Stavanger University Hospital
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Budapest、ハンガリー、1134
- Magyar Honvedseg Egeszsegugyi Kozpont
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Budapest、ハンガリー、1122
- Heart and Vascular Center of Semmelweis University
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Bron、フランス、69677
- Hopital Louis Pradel
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Montpellier、フランス、34295
- Hopital Arnaud de Villeneuve
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Nancy、フランス、54500
- CHRU NANCY
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Nantes、フランス、44093
- Hôpital Laennec
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Paris、フランス、75013
- Hôpital Pitie Salpétrière
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Paris、フランス、75015
- Georges Pompidou European Hospital
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Rouen、フランス、76031
- Hôpital Charles Nicolle
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Strasbourg、フランス、67000
- Hopitaux Universitaires de Strasbourg
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Toulouse、フランス、31000
- Clinique Pasteur
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Wroclaw、ポーランド、50981
- Clinical Military Hospital
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Łódź、ポーランド、94048
- NZOZ All-Med Centrum Medyczne
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria:
- A signed and dated informed consent form prior to any study procedure
- Adult male subjects and female subjects without childbearing potential.
- Clinical diagnosis of CHF with history of NYHA class II-III for at least 3 months before randomisation.
- Documented left ventricular ejection fraction (LVEF) < 40% measured by any modality within the previous 12 months in the subject's medical history.
- Subjects must also have at least one local measurement of BNP level ≥ 300 pg/mL or NT-proBNP level ≥ 1200 pg/mL (preferred assay, local laboratory) at the screening visit (maximum 7 days before randomisation).
- eGFR > 30 mL/min/1.73 m2 (MDRD) at screening.
- Serum potassium < 5.0 mmol/L at screening.
- Systolic blood pressure < 110 mmHg (average of 3 consecutive measurements) at screening.
- Prescribed to optimal pharmacologic therapy per "ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2016", or based on the updated current clinical practice, unless contra-indicated or not-tolerated, and on a stable dose for at least 30 days prior to enrolment (the dosage of the drugs cannot be increased or decreased respectively by more than double or half of initial dosage).
- Taking oral loop diuretics at doses < 250 mg furosemide daily (or equivalent).
Exclusion Criteria:
- BMI > 45 kg.m-2.
- Patients who require the use of HF IV therapy or oral furosemide > 250 mg (or equivalent) at any time during the 48 hours immediately before randomisation.
- Patients with unstable angina, myocardial infarction, PTCA, coronary artery bypass graft, cerebral vascular accident, or transient ischemic attack within previous 3 months (90 days) before enrolment.
- Patients whose primary cause of heart failure is mitral or aortic valve disease or congenital heart disease or hypertrophic obstructive cardiomyopathy or infiltrative cardiomyopathy (e.g. amyloidosis, sarcoidosis) or myocarditis.
- Patients with "new" permanent atrial fibrillation (AF), discovered within 3 months prior to randomization.
- Heart rate > 110 beats/min at screening.
- Patients scheduled for Pacemaker (including ICD, CRT), Angioplasty, CABG or LVAD within the next 3 months.
- Patients with severe documented chronic obstructive lung disease (COPD), defined as chronic need for oxygen therapy
- eGFR < 30 mL/min/1.73 m2 (MDRD) at screening.
- Decrease in eGFR greater than 20% within 3 weeks prior to the screening visit.
- Serum potassium > 5.0 mmol/L at screening.
- Systolic blood pressure < 110 mmHg or with signs or symptoms of hypotension.
- Symptomatic hypotension or orthostatic hypotension defined by a decrease of systolic blood pressure of more than 30 mm Hg in the standing vs. sitting position at screening and at the basal SBP of the D0 (before having taken the study medication).
- A marked baseline prolongation of QT/QTc interval (e.g. repeated demonstrated of a QTc interval > 450 ms) AND QRS < 100 ms. In case of QRS enlargement > 100 ms (i-e bundle branch block, pacemakers) QT does not accurately reflect repolarization and may not be calculated.
- A history of additional risk factors for Torsade de Pointes (TdP) (e.g. hypokalemia, family history of long QT Syndrome).
- The use of concomitant medications that prolong the QT/QTc interval.
- Insulin-requiring diabetic patients (including type 1 Diabetes).
- History of angioneurotic edema.
- Severe liver failure at screening defined by a value of ALAT and/or ASAT≥ 5 from the normal value.
- Patients involved in any interventional clinical study, patients enrolled in Registries and/or in non-interventional studies may participate.
- Patients who take an investigational or non-approved treatment.
- Women of childbearing potential.
- Patients with a prior cardiac transplant or patients currently on the list for cardiac transplantation.
- Patient with hypersensitivity to the active substance or to one of the other components of the trial preparation.
- Patients in whom an allergy requiring chronic treatment is known or exists.
- Patients with a history of previous illnesses of neurological or psychiatric nature that affect the Central Nervous System.
- Patients with a life expectancy of less than 12 months per physician judgment.
- Frail patient who, in the opinion of the investigator will not be able to follow the protocol.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：QGC001
QGC001 from 50mg to 500mg capsule twice daily, for 28 days, oral use
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プラセボコンパレーター：Placebo
Placebo, capsule twice daily, for 28 days, oral use
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Lactose capsule manufactured to mimic QGC001 50 mg and 250 mg
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Relative decrease in NT-proBNP
時間枠：28 days
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Percentage of subjects with a relative decrease in NT-proBNP of more than 30% from Baseline to day 28.
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28 days
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Blood pressure change
時間枠：28 days
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Blood pressure changes at each visit (D7, D14, D21, D28), compared to the Baseline measure
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28 days
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Blood biochemistry
時間枠：35 days
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blood biochemistry at D7, D14, D21, D28 and D35.
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35 days
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Urinary biochemistry
時間枠：35 days
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electrolytes, urinary osmolarity at D7, D14, D21, D28 and D35.
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35 days
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Change of NT-proBNP
時間枠：35 days
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Changes in central lab values of NT-proBNP at D7, D14, D21, D28 and D35.
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35 days
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Change of BNP
時間枠：35 days
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Changes in central lab values of BNP at D7, D14, D21, D28 and D35.
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35 days
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Change of selected biomarker levels
時間枠：28 days
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Changes in central lab values from baseline in selected biomarker levels (biomarkers involved in the pathophysiology of the disease, which will be decided later) at Day 7, Day 14, Day 21, Day 28
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28 days
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Quality of life Minnesota Living with Heart Failure Score
時間枠：28 days
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Quality of life Minnesota Living with Heart Failure Score and D0 and Day 28
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28 days
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
捜査官
- 主任研究者：Faiez Zannad, MD、Centre d'investigation clinique CHU-Nancy
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2016年6月1日
一次修了 (実際)
2018年9月12日
研究の完了 (実際)
2018年9月12日
試験登録日
最初に提出
2016年5月17日
QC基準を満たした最初の提出物
2016年5月20日
最初の投稿 (見積もり)
2016年5月23日
学習記録の更新
投稿された最後の更新 (実際)
2018年10月16日
QC基準を満たした最後の更新が送信されました
2018年10月11日
最終確認日
2018年10月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。