EGESTA - Emergent GI Therapy for Severe, Complicated CDI Using Fecal Microbiota Transplant (EGESTA)
EGESTA - Emergent GI Therapy for Severe, Complicated CDI Using Fecal Microbiota
The objectives/specific aims of this study are three-fold. First, the study seeks to evaluate the safety of fecal microbiota transplant (FMT) in patients with severe, complicated C. difficile infection (scCDI). Second, the study seeks to evaluate whether fecal microbiota transplant (FMT) can improve scCDI, with "improve" defined as either decreasing the severity of CDI, or by resolving the infection altogether. Third, the study seeks to further study the mechanism by which FMT improves the course of scCDI by performing 16S rRNA and ITS sequencing on pre-FMT and serial post-FMT stool samples in order to measure changes to bacterial and fungal microbiota as a consequence of CDI and FMT therapy. FMT material (hereafter referred to as FMTm) would be obtained from OpenBiome. FMTm is prepared from prescreened healthy donors.
The hypothesis of the study is that FMT is a preferred salvage therapy for scCDI as compared to (1) ongoing, failing medical therapy with conventional antibiotics and (2) surgery.
調査の概要
詳細な説明
The objectives/specific aims of this study are three-fold. First, the study seeks to evaluate the safety of fecal microbiota transplant (FMT) in patients with severe, complicated C. difficile infection (scCDI). Second, the study seeks to evaluate whether fecal microbiota transplant (FMT) can improve scCDI, with "improve" defined as either decreasing the severity of CDI, or by resolving the infection altogether. Third, the study seeks to further study the mechanism by which FMT improves the course of scCDI by performing 16S rRNA and ITS sequencing on pre-FMT and serial post-FMT stool samples in order to measure changes to bacterial and fungal microbiota as a consequence of CDI and FMT therapy. FMT material (hereafter referred to as FMTm) would be obtained from OpenBiome. FMTm is prepared from prescreened healthy donors.
The hypothesis of the study is that FMT is a preferred salvage therapy for scCDI as compared to (1) ongoing, failing medical therapy with conventional antibiotics and (2) surgery.
The standard of care treatment for scCDI is conventional antibiotics with either parenteral/oral metronidazole, and/or vancomycin provided in the form of oral and/or retention enemas. The reliability of these conventional antibiotics in the setting of scCDI is very unpredictable, and patients with CDI of this severity have a mortality rate that in some series is greater than 50%. It is against the mediocre historical record of these antibiotics that FMT would be tested in this highly moribund patient population.
FMT would not be provided to patients with scCDI off protocol.
研究の種類
段階
- 適用できない
連絡先と場所
研究場所
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Pennsylvania
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Hershey、Pennsylvania、アメリカ、17078
- David Stewart
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Adults between 18 years of age and 75 years of age.
- Have CDI defined as clinical symptoms of CDI (diarrhea with or without abdominal pain/abdominal distention) with a confirmatory nucleic acid amplification test (NAAT) positive for CDI.
Have severe/complicated disease as defined by ACG guidelines(appendix 1), with any of the following attributable to CDI:
- Admission to intensive care unit for CDI
- Hypotension (systolic blood pressure < 90 mmHg) with or without required use of vasopressors
- Fever ≥ 38.5 ° C
- Ileus (as defined by the absence of intestinal function for at least 24 hours and/or radiographic evidence of pathologically dilated small intestine without evidence of a mechanical obstruction) or significant abdominal distention
- Mental status changes
- WBC ≥ 35,000 cells / mm 3 or < 2,000 cells / mm 3
- Serum lactate levels >2.2 mmol / l
- End organ failure (mechanical ventilation,renal failure as defined by a rise in creatinine of >1.5 mg/dL either above the upper limit of normal for creatinine, or > 1.5 mg/dL from premorbid levels if that information is known, acute hepatic dysfunction as defined by an increase in AST or ALT to twice the upper limit of normal, etc.)
Exclusion Criteria:
- Pregnant or lactating women
- Prisoners
- Patients under the age of 18 or over the age of 76 years of age
Patients who are immunocompromised including but not limited to:
- Have HIV infection historically reported, regardless of CD4 count
- AIDS as defined by either an AIDS-defining diagnosis (appendix 2) or a CD4 count <200/mm3,
- Inherited or primary immune disorders,
- Received chemotherapy within the previous 90 days, or
- Current or recent treatment with any immunosuppressant medications in the past 90 days
- Individuals who have received FMT at any time before potential study enrollment
- Patients who do not have a stool test confirming C. difficile infection
- Patients who have a severe anaphylactic response to food
- Patients with allergies to sodium chloride or glycerol, both ingredients Generally Recognized As Safe (GRAS)
- Patients who have colorectal cancer
- Diagnosis of Irritable Bowel Disease or Irritable Bowel Syndrome
- Any other condition for which the Principal Investigator thinks the treatment may pose a health risk
- Anticipated or predicted death within the time period of follow-up for reasons unrelated to CDI
- An APACHE II score >29 at the time of evaluation for inclusion in the study protocol (Appendix 4.0)
- Mandatory ongoing antibiotic use for non-CDI infection
- Patients unable to provide informed consent or who do not have a legally authorized representative for consent
- Patients unable to comply with requirements of this study protocol
研究計画
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:なし
- 介入モデル:単一グループの割り当て
- 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 |
|---|---|
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実験的:fecal microbiota transplant
250 mL of fecal transplant material by enema as treatment
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Fecal microbiota transplant for the treatment of severe, complicated C. difficile infection
他の名前:
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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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Safety - adverse events
時間枠:Thirty days after treatment
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Absence of unexpected related adverse events
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Thirty days after treatment
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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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Efficacy (Cure of infection, or decrease in severity of infection based on white blood cell count)
時間枠:Thirty days after treatment
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Cure of infection, or decrease in severity of infection based on white blood cell count
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Thirty days after treatment
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協力者と研究者
協力者
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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