Detecting the Impact of Statin Therapy On Lowering Risk of Venous Thrombo-Embolic Events (DISOLVE) (DISOLVE)
6. července 2018 aktualizováno: Steven Ades, University of Vermont
Impact of Rosuvastatin on Risk Markers of Venous Thromboembolism During Systemic Therapy for Advanced Cancer
Patients with cancer have a high risk of developing venous blood clots or thromboembolism (VTE). In an effort to target patients at highest risk of VTE for thromboprophylaxis (protective treatment for blood clots), numerous studies have identified serum biomarkers for risk of future VTE. There is also increasing evidence pointing to a prophylactic effect of statin therapy on the risk of developing VTE in high-risk populations including patients with advanced cancer. The purpose of this research study is to find out whether treatment with rosuvastatin (the study drug) reduces the risk of VTE in patients with cancer receiving chemotherapy. This study is specifically investigating the impact of rosuvastatin therapy on serum biomarkers (D-dimer and others) that indicate a risk for VTE, as well as safety and tolerance of rosuvastatin therapy in this population.
This is a phase II randomized crossover study with two 3-4 week treatment periods during which all enrolled patients will receive 20 mg of rosuvastatin once a day by mouth or a matching placebo tablet. Approximately two tablespoons of blood will be collected for biomarker analysis at the beginning and end of each treatment period. After the first treatment period there will be a 3-5 week break where subjects will undergo a washout. Following this washout period every subject will "crossover" or begin taking the alternative therapy so everyone enrolled will receive the study drug either during the first or the second treatment period. Biomarker levels will be analyzed in both treatment periods and compared to baseline, with every patient acting as their own control.
Přehled studie
Postavení
Dokončeno
Intervence / Léčba
Typ studie
Intervenční
Zápis (Aktuální)
38
Fáze
- Fáze 2
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
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Vermont
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Burlington, Vermont, Spojené státy, 05401
- Fletcher Allen Health Care
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
18 let a starší (Dospělý, Starší dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Popis
Inclusion Criteria:
- Adult patients > 18 years old with locally-advanced or metastatic cancers who are about to start or are already receiving any systemic chemotherapy or targeted therapy.
- Estimated overall survival of ≥ 6 months
- Anticipated duration of therapy ≥ 9 weeks (if 3-week cycle) or ≥ 12 weeks (if 2 or 4-week cycle). Systemic therapy is allowed to change if necessary, or to terminate, during this period
Exclusion Criteria:
- Antithrombotic therapy including warfarin, dabigatran, low molecular weight heparin or unfractionated heparin. Patients taking aspirin may participate in this study.
- Anti-angiogenic therapy with thalidomide or lenalidomide. Patients receiving bevacizumab may participate in this study.
- Patients starting hormonal therapy exclusively, such as SERM or aromatase inhibitor therapy for breast cancer, or androgen-ablative therapy for prostate cancer.
- Statin use within 3 months prior to enrolment
- Adjuvant therapy in patients who have already received curative-intent local therapy (surgery or radiotherapy). Patients with glioblastoma starting adjuvant chemotherapy are an exception given the high likelihood of residual disease and risk of VTE in this population.
- Asian descent as assessed by history. If either of the participant's parents is Asian (peoples of East, Southeast, and South Asia), a patient will be excluded due to slower metabolism of the drug and concerns regarding toxicity at the 20 mg dose level.
- Urinary creatinine clearance of less than 40 ml/min based on reported MDRD GFR, present in FAHC metabolic profile reports, during the 14 day screening period.
- AST or ALT elevation of greater than 3X upper limit of normal, during the 14 day screening period.
- Patients with a known history of statin intolerance that was accompanied by severe adverse reaction.
- Patients who are currently participating in another clinical trial involving an investigational medication if there is a known or suspected drug interaction with rosuvastatin or the statin class, or if the investigational agent is known or suspected to be associated with a significantly increased risk of thrombosis.
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Prevence
- Přidělení: Randomizované
- Intervenční model: Crossover Assignment
- Maskování: Čtyřnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: Rosuvastatin First, Placebo Last
This arm will receive rosuvastatin during the first treatment period followed by placebo in the second treatment period after washout.
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20 mg po od
Ostatní jména:
20 mg po od
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Experimentální: Placebo First, Rosuvastatin Last
This arm will receive placebo during the first treatment period followed by rosuvastatin in the second treatment period after washout.
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20 mg po od
Ostatní jména:
20 mg po od
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Časové okno |
|---|---|
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To determine if rosuvastatin therapy reduces the risk of VTE in patients with cancer receiving chemotherapy, as measured by a decrease in D-dimer level with treatment compared to placebo
Časové okno: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
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baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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To investigate the impact of rosuvastatin therapy on other established biomarkers of VTE risk in cancer patients receiving chemotherapy as measured by the change in Factor VIII
Časové okno: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
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baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
|
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To investigate the impact of rosuvastatin therapy on other established biomarkers of VTE risk in cancer patients receiving chemotherapy as measured by the change in soluble P-selectin
Časové okno: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
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baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
|
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To investigate the impact of rosuvastatin therapy on other established biomarkers of VTE risk in cancer patients receiving chemotherapy as measured by the change in C-reactive protein
Časové okno: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
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baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
|
|
To investigate the impact of rosuvastatin therapy on other established biomarkers of VTE risk in cancer patients receiving chemotherapy as measured by the change in Peak thrombin generation
Časové okno: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
|
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Adverse Events (CTCAE v4) associated with rosuvastatin therapy
Časové okno: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
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Liver toxicity and rhabdomyolysis
|
baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
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Venous thromboembolism
Časové okno: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
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Clinical signs of venous thromboembolism
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baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
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To investigate the impact of rosuvastatin therapy on other established biomarkers of VTE risk in cancer patients receiving chemotherapy as measured by the change in Plasminogen activator inhibitor-1 activity
Časové okno: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
|
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To investigate the impact of rosuvastatin therapy on other established biomarkers of VTE risk in cancer patients receiving chemotherapy as measured by the change in Plasminogen activator inhibitor-1 protein concentration
Časové okno: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
|
|
To investigate the impact of rosuvastatin therapy on other established biomarkers of VTE risk in cancer patients receiving chemotherapy as measured by the change in tissue factor
Časové okno: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
|
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To investigate the impact of rosuvastatin therapy on other established biomarkers of VTE risk in cancer patients receiving chemotherapy as measured by the change in Factor XIa
Časové okno: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Vyšetřovatelé
- Vrchní vyšetřovatel: Steven Ades, MD, MSc, University of Vermont
Publikace a užitečné odkazy
Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.
Užitečné odkazy
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia
1. března 2012
Primární dokončení (Aktuální)
1. července 2016
Dokončení studie (Aktuální)
1. září 2016
Termíny zápisu do studia
První předloženo
20. ledna 2012
První předloženo, které splnilo kritéria kontroly kvality
30. ledna 2012
První zveřejněno (Odhad)
2. února 2012
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
10. července 2018
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
6. července 2018
Naposledy ověřeno
1. července 2018
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Kardiovaskulární choroby
- Cévní onemocnění
- Embolie a trombóza
- Trombóza
- Žilní trombóza
- Tromboembolismus
- Žilní tromboembolismus
- Molekulární mechanismy farmakologického působení
- Inhibitory enzymů
- Antimetabolity
- Anticholesteremická činidla
- Hypolipidemická činidla
- Látky regulující lipidy
- Inhibitory hydroxymethylglutaryl-CoA reduktázy
- Rosuvastatin Vápník
Další identifikační čísla studie
- VCC 1110
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .