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Trial record 98 of 591 for:    WARFARIN

Sirolimus Combined With Low-dose Warfarin for the Treatment of Refractory PNH

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ClinicalTrials.gov Identifier: NCT03866681
Recruitment Status : Not yet recruiting
First Posted : March 7, 2019
Last Update Posted : March 8, 2019
Sponsor:
Information provided by (Responsible Party):
Bing Han, Peking Union Medical College Hospital

Brief Summary:
Classical paroxysmal nocturnal hemoglobinuria(PNH) is mainly characterized by hemolysis and thrombosis, which reduced patients ' quality of life(QoL) greatly and even lead to death. Glucocorticoids and symptomatic supportive therapy are traditional treatments and the response rate is far from satisfactory. Eculizumab is an effective therapy but it is expensive and not available in China mainland.The investigators aim to explore the efficacy and safety of sirolimus for refractory classic PNH.

Condition or disease Intervention/treatment Phase
Paroxysmal Nocturnal Hemoglobinuria Drug: sirolimus Phase 4

Detailed Description:

Classical paroxysmal nocturnal hemoglobinuria(PNH) is mainly characterized by hemolysis and thrombosis, which reduced patients ' quality of life(QoL) greatly and even lead to death. There is no ideal therapy except for eculizumab, expensive and not available in China mainland. Glucocorticoids and symptomatic supportive therapy are traditional treatments. The response rate is 30%, far from satisfactory. In recent years, T lymphocyte-mediated destruction of normal hematopoietic stem cells have been reported to involve the pathogenesis of PNH, making immunomodulatory drugs be potential effective treatments.

Sirolimus (rapamycin), produced by the bacterium Streptomyces hygroscopicus, is a mammalian target of Rapamycin (mTOR) inhibitor. mTOR is a serine/threonine kinase that regulates cell growth, proliferation, metabolism and survival. It has two interacting complex, mTORC1 and mTORC2. Sirolimus primarily inhibits mTORC1, has been demonstrated for its immunomodulatory effects and ability to improve hematopoietic stem cell function. Recently, sirolimus has been reported to be effective and well tolerated in the treatment of immune-mediated cytopenias, even in multi-immunosuppressants resistant patients. In addition, classical PNH patients have a higher risk of thrombosis especially in refractory ones and it is reasonable to use low-dose warfarin in the management of patients with classic refractory PNH.

In this study, it is anticipated to evaluate the effect of sirolimus combined with low-dose warfarin on patients with refractory classic PNH. The adverse effects and QoL on different time points were documented.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Sirolimus Combined With Low-dose Warfarin for the Treatment of Refractory Classic Paroxysmal Nocturnal Hemoglobinuria ,a Prospective Study
Estimated Study Start Date : April 1, 2019
Estimated Primary Completion Date : March 1, 2021
Estimated Study Completion Date : April 1, 2022


Arm Intervention/treatment
Experimental: Patients cohort
A total of 40 patients with refractory classic PNH will be included and will be intervened by a combined therapy including sirolimus and low-dose warfarin
Drug: sirolimus
The dose of sirolimus is adjusted according to monitored serum concentration, maintain Rapamycin concentration ranging from 4 to 10ng/ml.Warfarin was administered orally at a dose of 1mg per day for a year,then gradually reduced to stop.
Other Name: warfarin




Primary Outcome Measures :
  1. Hemoglobin [ Time Frame: 2 years ]
    Hemoglobin in g/L


Secondary Outcome Measures :
  1. Short Form 36 items(SF-36) questionnaire [ Time Frame: 2 years ]
    SF-36 questionnaire in scores



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • age 18-70 years
  • diagnosed with PNH and no thrombosis
  • ineffective, relapsed or intolerant to conventional treatment (eg glucocorticoids, • • iron, folic acid, androgen, etc.)
  • not available for hematopoietic stem cell transplantation
  • ECOG≤2
  • agreed to sign the consent forms

Exclusion Criteria:

  • severe heart, liver and kidney dysfunction
  • combined with thrombotic complications
  • people who are pregnant and breastfeeding
  • history of other immunosuppressive agents in recent 3 months
  • Patients who are not eligible to participate in this trial due to any reason based • • • on the consideration of investigator

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03866681


Locations
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China
Peking union medical college hospital Not yet recruiting
Beijing, China
Contact: Bing Han, Doctor    +86-010-69155760    hanbing_li@sina.com   
Sponsors and Collaborators
Peking Union Medical College Hospital

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Responsible Party: Bing Han, Clinical Professor, Peking Union Medical College Hospital
ClinicalTrials.gov Identifier: NCT03866681     History of Changes
Other Study ID Numbers: hanb
First Posted: March 7, 2019    Key Record Dates
Last Update Posted: March 8, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Warfarin
Hemoglobinuria
Hemoglobinuria, Paroxysmal
Proteinuria
Urination Disorders
Urologic Diseases
Urological Manifestations
Signs and Symptoms
Anemia, Hemolytic
Anemia
Hematologic Diseases
Myelodysplastic Syndromes
Bone Marrow Diseases
Sirolimus
Everolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anticoagulants