CMV Antiviral Prevention Strategies in D+R-Liver Transplants ("CAPSIL")
Prophylaxis Versus Preemptive Therapy for the Prevention of CMV in High-Risk R-D+ Liver Transplant Recipients
This is a trial of preemptive therapy vs. prophylaxis for prevention of Cytomegalovirus (CMV) disease in R-D+ liver transplant patients.
Subjects will be randomized within 10 days of transplant to receive in an open label design, either antiviral prophylaxis with valganciclovir, 900 mg orally once daily or preemptive therapy (weekly monitoring for CMV viremia by plasma PCR) for 100 days post-randomization with initiation of oral valganciclovir 900mg orally twice daily at onset of CMV viremia and continued until plasma PCR is negative on two consecutive weekly PCR tests).
A minimum of 176 subjects will be enrolled in the study.
The study duration is 7 years.
The primary objective of this study is to compare prophylaxis versus preemptive therapy using valganciclovir for the prevention of CMV disease in R-/D+ liver transplant recipients.
調査の概要
詳細な説明
This is a prospective, randomized, multicenter trial of preemptive therapy vs. prophylaxis for prevention of Cytomegalovirus (CMV) disease in seronegative recipient- seropositive donor (R-D+) liver transplant patients.Subjects will be randomized within 10 days of transplant to receive in an open label design, either antiviral prophylaxis with valganciclovir 900 mg orally once daily or preemptive therapy for 100 days post-randomization with initiation of oral valganciclovir 900mg orally twice daily at onset of CMV viremia (monitored weekly) and continued until plasma PCR is negative on two consecutive weekly PCR tests.
Study participants will be followed during the intervention period (100 days post randomization) and until 12 months post-transplant for CMV disease, toxicity, and clinical outcomes (opportunistic infections, rejection, graft loss and mortality).
Drug safety labs will be assessed and recorded for the entire treatment period in both the prophylaxis and preemptive group.
Re-transplantation and all-cause mortality will also be assessed at study closure and no longer than 5 years after enrollment.
Additionally, the impact of the two CMV prevention strategies on CMV-specific cellular and humoral immune responses will be evaluated at 100 days after randomization, and 6 and 12 months post-transplant.
A minimum of 176 subjects will be enrolled in the study.
Allowing for over-enrollment to replace dropouts, up to 205 subjects may be enrolled to achieve the target enrollment of 176.
Subjects will be randomized into one of the two groups in 1:1 ratio.
The study duration is 7 years.
The primary objective of this study is to compare prophylaxis versus preemptive therapy using valganciclovir for the prevention of CMV disease in R-/D+ liver transplant recipients.
The secondary objectives are:1) to assess the two preventive strategies for clinical outcomes (major bacterial, fungal and non-CMV viral infections, rejection, graft loss and mortality) at one year post transplantation; 2) to assess the two preventive strategies for hematologic toxicity (assessment of neutropenia and receipt of hematopoietic growth factor during study days 1-107).
研究の種類
介入
入学 (実際)
205
段階
- フェーズ 4
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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California
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Los Angeles、California、アメリカ、90095-8358
- Ronald Reagan University of California Los Angeles Medical Center
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Georgia
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Atlanta、Georgia、アメリカ、30322-1013
- Emory Clinic - Transplant Center
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Minnesota
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Rochester、Minnesota、アメリカ、55905-0001
- Mayo Clinic, Rochester - Infectious Diseases
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New York
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New York、New York、アメリカ、10029-6504
- Mount Sinai School of Medicine - Medicine - Infectious Diseases
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Pennsylvania
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Pittsburgh、Pennsylvania、アメリカ、15213-3403
- University of Pittsburgh - Medicine - Infectious Diseases
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Washington
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Seattle、Washington、アメリカ、98195-7110
- University of Washington - Medicine
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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～99年 (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:
- Be > / = 18 years of age.
- Have negative Cytomegalovirus (CMV) serology (confirmed within 6 months of transplant) and receive a liver from a donor with positive CMV serology (R-/D+).
- Have received their first orthotopic liver transplant (the transplanted liver may be deceased donor or live donor graft) within 10 days prior.
- Have absolute neutrophil count > 1000/µL at randomization.
- If female, and not postmenopausal or surgically sterile, must have negative pregnancy test (serum or urine) within 48 hours prior to randomization and must also agree to use medically approved method of contraception. Acceptable methods include: barrier method, intrauterine device (hormonal or non-hormonal), oral hormonal contraceptives, abstinence for 100 days after randomization and 3 months after valganciclovir cessation.
-- If male, and has not had a vasectomy, he must agree to practice barrier method of contraception for 100 days after randomization and 3 months after valganciclovir cessation.
- Subject or legally authorized representative has provided written informed consent.
Exclusion Criteria:
- Currently enrolled in any interventional trial of an investigational therapeutic agent unless co-enrollment has been approved by study Principal Investigators (PIs) and the DMID prior to enrollment.
- Have hypersensitivity to acyclovir, ganciclovir or valganciclovir.
- Be breast-feeding mother.
- Have known Human immunodeficiency virus (HIV) infection (based on testing performed during the transplant evaluation process).
- Be undergoing multi organ transplant or have undergone prior organ transplant.
- Have expected life expectancy of less than 72 hours.
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：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Preemptive Therapy
900 mg of Valganciclovir given orally twice daily to Preemptive Therapy subjects upon detection of CMV viremia until plasma PCR is negative on two consecutive weekly PCR test.
All dosages adjusted for renal dysfunction.
n=88
|
Valganciclovir, 900 mg given orally once daily to all Prophylaxis group subjects for 100 days post transplantation as prophylaxis.
Valganciclovir, 900 mg given orally twice daily to Preemptive Therapy group subjects as a PET only after a positive CMV PCR test and stopped after PCR is negative for 2 consecutive weeks.
|
|
アクティブコンパレータ：Prophylaxis
900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation.
All dosages adjusted for renal dysfunction.
n=88
|
Valganciclovir, 900 mg given orally once daily to all Prophylaxis group subjects for 100 days post transplantation as prophylaxis.
Valganciclovir, 900 mg given orally twice daily to Preemptive Therapy group subjects as a PET only after a positive CMV PCR test and stopped after PCR is negative for 2 consecutive weeks.
|
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 |
|---|---|---|
|
Incidence of Cytomegalovirus (CMV) Disease.
時間枠：365 days post-transplant
|
CMV disease as verified by an independent end point committee
|
365 days post-transplant
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
All-cause Mortality
時間枠：Up to 365 days post-transplant
|
Survival probability at 1 year
|
Up to 365 days post-transplant
|
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Incidence of Allograft Rejection
時間枠：Up to 365 days post-transplant
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Number of subjects with allograft rejection
|
Up to 365 days post-transplant
|
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Graft Loss
時間枠：Up to 365 days post-transplant
|
Incidence of graft loss (re-transplantation)
|
Up to 365 days post-transplant
|
|
Late-onset CMV Disease
時間枠：Up to 365 days post-transplant
|
Incidence of late-onset CMV disease (occurring after 100 days post-randomization) as adjudicated by end point committee
|
Up to 365 days post-transplant
|
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Bacterial Infections
時間枠：Up to 365 days post-transplant
|
Incidence of bacterial opportunistic infections
|
Up to 365 days post-transplant
|
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Major Fungal Infections
時間枠：Up to 365 days post-transplant
|
Opportunistic fungal infections
|
Up to 365 days post-transplant
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Major Non-CMV Viral Infections
時間枠：Up to 365 days post-transplant
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Incidence of non-CMV viral infections
|
Up to 365 days post-transplant
|
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Neutropenia
時間枠：Day 1 through Day 107
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Incidence of neutropenia less than 1000/µL while on valganciclovir treatment
|
Day 1 through Day 107
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Neutropenia Less Than 500
時間枠：prior to day 107
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ANC less than 500 while on valganciclovir
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prior to day 107
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Hematopoietic Growth Factors
時間枠：Day 1 through Day 107
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Hematopoietic growth factor receipt for ANC less than 500 during valganciclovir treatment.
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Day 1 through Day 107
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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。
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- Singh N, Winston DJ, Razonable RR, Lyon GM, Silveira FP, Wagener MM, Limaye AP. Risk Factors for Cytomegalovirus Viremia following Liver Transplantation With a Seropositive Donor and Seronegative Recipient Receiving Antiviral Therapy. J Infect Dis. 2021 Mar 29;223(6):1073-1077. doi: 10.1093/infdis/jiaa470.
- Singh N, Winston DJ, Razonable RR, Lyon GM, Silveira FP, Wagener MM, Stevens-Ayers T, Edmison B, Boeckh M, Limaye AP. Effect of Preemptive Therapy vs Antiviral Prophylaxis on Cytomegalovirus Disease in Seronegative Liver Transplant Recipients With Seropositive Donors: A Randomized Clinical Trial. JAMA. 2020 Apr 14;323(14):1378-1387. doi: 10.1001/jama.2020.3138.
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 (実際)
2012年10月29日
一次修了 (実際)
2018年6月22日
研究の完了 (実際)
2018年6月22日
試験登録日
最初に提出
2012年3月2日
QC基準を満たした最初の提出物
2012年3月8日
最初の投稿 (見積もり)
2012年3月13日
学習記録の更新
投稿された最後の更新 (実際)
2021年8月26日
QC基準を満たした最後の更新が送信されました
2021年7月29日
最終確認日
2018年3月22日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 11-0073
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
はい
米国FDA規制機器製品の研究
いいえ
米国で製造され、米国から輸出された製品。
いいえ
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。