NCT Number: NCT07127718
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
Interested in participating?
Request Info18 year–60 year
All sexes
Interventional
Phase 2
Institute of Human Genetics, National Institutes of Health - University of the Philippines Manila, Manila, National Capital Region, Philippines
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.
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
ABO/Rh-type compatible fresh frozen plasma (FPP) units will be thawed to 37° prior to administration. Plasma transfusion will be administered intravenously, 1 unit for 4 hours every 12 hours. There will be two consecutive days for the transfusion for a total of 4 units.
Other names: Prophylactic Plasma Component Transfusion, Plasma Transfusion, Prophylactic Plasma Component Therapy, PPT
The hemoperfusion (HP) procedure will follow the standard procedure of National Kidney and Transplant Institute (NKTI) using Jafron HA330 hemoperfusion cartridge. First, an internal jugular catheter is attached to the patient. Alternatively, an arteriovenous fistula or arteriovenous graft may be placed on the patient. The patient will then be hooked to a hemodialysis machine. Blood pump speed will be set to 150-200mL/min, and HP will last for 2 to 2.5 hours. Whole blood will flow through the sorbent HA330 cartridge and back to the patient. Anticoagulation is not necessary due to the short treatment time. Hemoperfusion will be repeated after 12-24 hours for at least three days.
Other names: HP
A veno-venous ECMO (VV ECMO) will be applied by aseptically inserting a venous cannula into the femoral veins. The patients will be hooked to an ECMO machine. Patients without significant bleeding or vascular intervention will be managed with an activated clotting time set at 140-180 sec by 800-1000 U/h of heparin. Otherwise, heparin will be titrated to maintain a partial thromboplastin time of 60-80 sec.
ECMO settings are as follows:
Criteria for weaning:
Other names: ECMO
Conventional therapy for leptospirosis includes antibiotics, fluids, inotropes, renal replacement therapy, ventilator support, and other treatment that the attending physician deems necessary.
Other names: Standard of care
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: From admission to discharge from the hospital, assessed up to study completion, an average of 3 years
Number of days requiring dialysis during hospital stay.
Time frame: From admission to discharge from the hospital, assessed up to study completion, an average of 3 years
Number of days requiring inotropic support to attain MAP >65 and number of days requiring each inotrope
Time frame: From admission to discharge from the hospital, assessed up to study completion, an average of 3 years
Inability to maintain Sp02 >92% on maximum non-invasive respiratory support
Time frame: From admission to discharge from the hospital, assessed up to study completion, an average of 3 years
Occurrence of systolic blood pressure less than 90 mm Hg, OR mean arterial pressure less than 65 mm Hg, OR a decrease of 40 mm Hg in systolic blood pressure compared to baseline: unresponsive to crystalloid fluid challenge of 20 to 40 mL/kg OR requiring vasopressor support
Time frame: 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 severe acute kidney injury as indicated by the need for emergency dialysis due to intractable acidosis, hyperkalemia, uremic encephalopathy or pericarditis.
Time frame: From admission to discharge from the hospital, assessed up to study completion, an average of 3 years
A participant is considered for Extracorporeal Membrane Oxygenation (ECMO) when he/she attains a Murray score of greater than or equal to 2.75.
The Murray score is a scale used to assess the severity of acute lung injury in acute respiratory distress syndrome (ARDS). A Murray score of 0 means there is no lung injury; a score of 0.1-2.5 means there is mild to moderate lung injury; and a score of greater than 2.5 means there is severe lung injury.
Time frame: From admission to discharge from the hospital, assessed up to study completion, an average of 3 years
A participant is considered for Extracorporeal Membrane Oxygenation (ECMO) when he/she attains the a Horowitz Index for Lung Function (P/F Ratio) of less than 200.
The Horowitz Index for Lung Function (P/F Ratio) is the ratio of arterial oxygen partial pressure (PaO2) and the fractional inspired oxygen (FiO2). A P/F ratio of greater than 300 mmHg indicates absence of ARDS; 201-300 mmHg is mild ARDS; 101-200 mmHg is moderate ARDS; and less than or equal to 100 is severe ARDS.
Time frame: From admission into ICU to date out of ICU, assessed up to study completion, an average of 3 years
Number of days patient is required to stay in ICU (date out of ICU will be date ordered by the attending physician)
Contact information is provided by the study sponsor or research team.
National Kidney and Transplant Institute, Philippines
Other
Decreasing Leptospirosis Emergence Through Prognosis and Treatment Optimization (DeLEPTO) Project 1: Preventive Strategies for Early and Late Complications of Leptospirosis
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
Published trials that share one or more normalized conditions with this study.
NCT07358910
Adenophorea Infections, Adenoviridae Infections
Phnom Penh, Cambodia
View Trial DetailsNCT04288674
Bacterial Infections, Bacterial Infections and Mycoses
Cologne, North Rhine-Westphalia, Germany
View Trial DetailsNCT05425524
Bacterial Infections, Bacterial Infections and Mycoses
Bangkok, Thailand
View Trial DetailsNCT07611591
Bacterial Infections, Bacterial Infections and Mycoses
View Trial Details