Decreasing Leptospirosis Emergence Through Prognosis and Treatment Optimization (DeLEPTO) Project 1: Preventive Strategies for Early and Late Complications of Leptospirosis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 678
- 试验地点
- 5
- 主要终点
- Presence of Significant Pulmonary Involvement
研究概览
简要总结
The goal of this clinical trial is to learn if complement factor I (CFI) works to predict development of complications in participants with leptospirosis. It will also learn if plasma transfusion, hemoperfusion, and extracorporeal membrane oxygenation works to treat participants with leptospirosis. The main questions it aims to answer are:
- Does a low level of CFI predict the development of lung damage in participants with leptospirosis?
- Does plasma tranfusion lower the chances of participants getting lung damage from leptospirosis?
- Does hemoperfusion work to remove harmful materials from the blood of participants with leptospirosis?
- Does extracorporeal membrane oxygenation increase the chance of survival in participants with lung damage?
Researchers will compare plasma tranfusion and hemoperfusion to conventional therapy (standard of care for leptospirosis, including antibiotics, fluids, and other treatment that the doctor deems necessary) to see if these novel therapies work to treat leptospirosis.
Participants will:
- Give blood samples for the study of CFI
- Receive conventional therapy and/or plasma transfusion for 4 times in 2 days, OR
- Receive conventional therapy and/or hemoperfusion for at least 3 days, AND/OR
- Receive extracorporeal membrane oxygenation if their condition worsens
详细描述
This study aims to determine the clinical utility of complement factor I (CFI) as a prognosticator in patients with complicated leptospirosis without severe pulmonary complications and to determine if its guidance to preemptive measures can lead to a reduction in adverse clinical outcomes, specifically the occurrence of pulmonary bleeding and acute respiratory distress syndrome (ARDS), and mortality. Hence, the results of the study may lead to novel treatment approaches that can be readily applied in clinical practice. The decision to provide preemptive non-invasive therapies or early intensive care admission could lead to significant breakthroughs in managing the disease.
Within the Decreasing Leptospirosis Emergence through Prognosis and Treatment Optimization (DeLEPTO) program's vision of developing tools to increase the survival of leptospirosis patients, this project will explore the avenue of novel tertiary care. Specifically, the program will look into the possibility of CFI repletion using plasma transfusion, cytokine depletion strategies using hemoperfusion (HP), and extracorporeal membrane oxygenation (ECMO). It would be interesting to see how such interventions could work individually or in a pipeline with other proposed interventions. In addition to plasma therapy, ECMO was observed to improve outcomes in severe leptospirosis. As a secondary endpoint, it would also be interesting to know if CFI can prognosticate who will benefit the most from such interventions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with acute fever (38ºC for at least two days) and at least one of the following: myalgia, jaundice, headache, meningeal irritation, oliguria, conjunctival suffusion
- •Who have a microscopic agglutination test (MAT) that indicates a single serum sample MAT titer greater than or equal to 1:400
- •Or a positive result for the latex agglutination test or a repeat test after seven days
- •Or a positive result for Leptospira IgG/IgM lateral flow immunochromatographic test (ICT) or a repeat test within 3-14 days after the baseline test
- •Or a positive result for Leptospira polymerase chain reaction (PCR)
- •Or a positive blood culture of leptospira WITHOUT the complication specified in a subgroup of interest
- •PPTTRT/PPTCONV: Not requiring ventilator support
- •HPTRT/HPCONV: Dialysis Requiring Acute Kidney Injury. Defined as KDIGO Acute Kidney Injury Stage 3 or requiring renal replacement therapy to correct intractable acidosis, electrolyte abnormality, or over uremic encephalopathy or pericarditis
- •HPTRT/HPCONV: Vasopressor Requiring - The subject must have received intravenous fluid resuscitation of a minimum of 30ml/kg within 24 hours of eligibility and still with hypotension (blood pressure less than 90/60, MAP less than 65) requiring vasopressor support
- •HPTRT/HPCONV: SOFA SCORE less than 15
- •ECMO: A Murray score of greater than or equal to 2.75
排除标准
- •Previous diagnosis of chronic kidney disease or on maintenance dialysis
- •Previous diagnoses of diseases associated with hemoptysis, such as bronchiectasis
- •Blood dyscrasias, malignancy, severe heart disease, HIV, cavitary PTB, Cirrhosis by ultrasound, severe malnutrition (Weight of less than 35kg)
- •Post cardiac arrest or those with GCS less than 8 at present. Participant has had chest compressions or CPR
- •Pregnancy
- •PPTTRT/PPTCONV: Requiring emergent dialyses
- •PPTTRT/PPTCONV: Significant lung pathology as defined by P/F ratio less than 300, or obvious respiratory distress
- •PPTTRT/PPTCONV: Presence of severe neurological symptoms
- •PPTTRT/PPTCONV: Hypotension (or need for vasopressor support)
- •PPTTRT/PPTCONV: Ongoing hemodynamic instability
研究组 & 干预措施
Prophylactic Plasma Component Therapy with Conventional Treatment (PPTTRT)
This serves as the case arm for prophylactic plasma transfusion (PPT).
Participants in the PPTTRT arm will receive transfusion if the peripheral blood mononuclear cell (PBMC) complement factor I (CFI) quantitative real-time polymerase chain reaction (qPCR) deltaCT is found to be at least 25 or more. These participants will also be receiving standard of care treatment.
Participants in the PPTTRT arm with PBMC CFI qPCR deltaCT less than 25 will only be receiving standard of care treatment.
If a participant is found to have a Murray score of greater than or equal to 2.75 over the course of the hospital stay, they will undergo extracorporeal membrane oxygenation (ECMO).
干预措施: Prophylactic Plasma Transfusion (Biological)
Prophylactic Plasma Component Therapy with Conventional Treatment (PPTTRT)
This serves as the case arm for prophylactic plasma transfusion (PPT).
Participants in the PPTTRT arm will receive transfusion if the peripheral blood mononuclear cell (PBMC) complement factor I (CFI) quantitative real-time polymerase chain reaction (qPCR) deltaCT is found to be at least 25 or more. These participants will also be receiving standard of care treatment.
Participants in the PPTTRT arm with PBMC CFI qPCR deltaCT less than 25 will only be receiving standard of care treatment.
If a participant is found to have a Murray score of greater than or equal to 2.75 over the course of the hospital stay, they will undergo extracorporeal membrane oxygenation (ECMO).
干预措施: Extracorporeal Membrane Oxygenation (Device)
Prophylactic Plasma Component Therapy with Conventional Treatment (PPTTRT)
This serves as the case arm for prophylactic plasma transfusion (PPT).
Participants in the PPTTRT arm will receive transfusion if the peripheral blood mononuclear cell (PBMC) complement factor I (CFI) quantitative real-time polymerase chain reaction (qPCR) deltaCT is found to be at least 25 or more. These participants will also be receiving standard of care treatment.
Participants in the PPTTRT arm with PBMC CFI qPCR deltaCT less than 25 will only be receiving standard of care treatment.
If a participant is found to have a Murray score of greater than or equal to 2.75 over the course of the hospital stay, they will undergo extracorporeal membrane oxygenation (ECMO).
干预措施: Conventional therapy (Other)
Conventional Treatment (PPTCONV)
This serves as the control arm for prophylactic plasma transfusion (PPT).
Participants in the PPTCONV arm will only be receiving standard of care treatment.
If a participant is found to have a Murray score of greater than or equal to 2.75 over the course of the hospital stay, they will undergo extracorporeal membrane oxygenation (ECMO).
干预措施: Extracorporeal Membrane Oxygenation (Device)
Conventional Treatment (PPTCONV)
This serves as the control arm for prophylactic plasma transfusion (PPT).
Participants in the PPTCONV arm will only be receiving standard of care treatment.
If a participant is found to have a Murray score of greater than or equal to 2.75 over the course of the hospital stay, they will undergo extracorporeal membrane oxygenation (ECMO).
干预措施: Conventional therapy (Other)
Hemoperfusion Treatment with Conventional Treatment (HPTRT)
This serves as the case arm for hemoperfusion (HP).
Participants in the HPTRT arm will receive hemoperfusion and standard of care.
Participants with a Murray score of greater than or equal to 2.75 will undergo extracorporeal membrane oxygenation (ECMO) as a rescue treatment.
干预措施: Hemoperfusion (Device)
Hemoperfusion Treatment with Conventional Treatment (HPTRT)
This serves as the case arm for hemoperfusion (HP).
Participants in the HPTRT arm will receive hemoperfusion and standard of care.
Participants with a Murray score of greater than or equal to 2.75 will undergo extracorporeal membrane oxygenation (ECMO) as a rescue treatment.
干预措施: Extracorporeal Membrane Oxygenation (Device)
Hemoperfusion Treatment with Conventional Treatment (HPTRT)
This serves as the case arm for hemoperfusion (HP).
Participants in the HPTRT arm will receive hemoperfusion and standard of care.
Participants with a Murray score of greater than or equal to 2.75 will undergo extracorporeal membrane oxygenation (ECMO) as a rescue treatment.
干预措施: Conventional therapy (Other)
Conventional Treatment (HPCONV)
This serves as the control arm for hemoperfusion (HP).
Participants in the HPCONV arm will only be receiving standard of care.
Participants with a Murray score of greater than or equal to 2.75 will undergo extracorporeal membrane oxygenation (ECMO) as a rescue treatment.
干预措施: Extracorporeal Membrane Oxygenation (Device)
Conventional Treatment (HPCONV)
This serves as the control arm for hemoperfusion (HP).
Participants in the HPCONV arm will only be receiving standard of care.
Participants with a Murray score of greater than or equal to 2.75 will undergo extracorporeal membrane oxygenation (ECMO) as a rescue treatment.
干预措施: Conventional therapy (Other)
结局指标
主要结局
Presence of Significant Pulmonary Involvement
时间窗: From admission to discharge from the hospital, assessed up to study completion, an average of 3 years
As in leptospirosis (Weil's syndrome) plus evidence of pulmonary injury as indicated by (1) the need for mechanical ventilator support, (2) P/F ratio \<200,(3) gross hemoptysis, OR (4) chest x-ray result consistent with leptospirosis-related pulmonary changes.
Determination of CFI levels via qPCR and via ELISA
时间窗: At baseline and Day 1 post-treatment, assessed up to study completion, an average of 3 years
Baseline blood samples will be obtained for CFI qPCR and ELISA upon enrollment. Post-treatment blood samples will be obtained for ELISA. Correlation of values of qPCR results to ELISA data will be performed using Pearson correlation (r2 of 0.80 or higher will be considered highly correlated). Test for concordance using Kendall's W will be done.
Hospital Days
时间窗: From admission to discharge from the hospital, assessed up to study completion, an average of 3 years
Hospital days will be computed from the date of admission to the date of discharge. Mortality or discharge against medical advice will be penalized with a maximum stay of at least 30 days.
Occurrence of Mortality
时间窗: From admission to discharge from the hospital or date of death, assessed up to study completion, an average of 3 years
Mortality is defined as death occurring to be related to the natural course of the present condition of leptospirosis or its complication, but not more than two weeks upon discharge by attending physician after being assessed as well recovered, or the like.
次要结局
- Need for Inotropic Support(From admission to discharge from the hospital, assessed up to study completion, an average of 3 years)
- Need for Renal Replacement Therapy(From admission to discharge from the hospital, assessed up to study completion, an average of 3 years)
- Need for Emergent Invasive Respiratory Support(From admission to discharge from the hospital, assessed up to study completion, an average of 3 years)
- Presence of Significant Renal Involvement(From admission to discharge from the hospital, assessed up to study completion, an average of 3 years)
- Need for Extracorporeal Membrane Oxygenation (ECMO) assessed via Murray score(From admission to discharge from the hospital, assessed up to study completion, an average of 3 years)
- Presence of Refractory Hypotension(From admission to discharge from the hospital, assessed up to study completion, an average of 3 years)
- Need for Extracorporeal Membrane Oxygenation (ECMO) assessed via Horowitz Index for Lung Function (P/F Ratio)(From admission to discharge from the hospital, assessed up to study completion, an average of 3 years)
- Intensive Care Unit (ICU) Days(From admission into ICU to date out of ICU, assessed up to study completion, an average of 3 years)
研究者
Romina A. Danguilan
Deputy Executive Director for Medical Services
National Kidney and Transplant Institute, Philippines