Preventive Strategies for Early and Late Complications of Leptospirosis

Decreasing Leptospirosis Emergence Through Prognosis and Treatment Optimization (DeLEPTO) Project 1: Preventive Strategies for Early and Late Complications of Leptospirosis

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

Study Overview

• Status: Recruiting
• Conditions: Leptospirosis
• Intervention / Treatment: Biological: Prophylactic Plasma Transfusion; Device: Extracorporeal Membrane Oxygenation; Other: Conventional therapy; Device: Hemoperfusion

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 678
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Romina Danguilan, MD; Phone Number: 1004 (63)(02)8981-0300; Email: radanguilan@gmail.com

Study Locations

• Philippines
  • National Capital Region
    • Manila, National Capital Region, Philippines, 1000
      • Active, not recruiting
      • Institute of Human Genetics, National Institutes of Health - University of the Philippines Manila
    • Manila, National Capital Region, Philippines, 1003
      • Recruiting
      • San Lazaro Hospital
      • Contact: Rontgene M Solante, MD; Phone Number: (63)(02)5309-9608; Email: rontgenesolante@gmail.com
      • Principal Investigator: Rontgene M Solante, MD
      • Sub-Investigator: Ana Ria Sayo-Abungan, MD
      • Sub-Investigator: Jeffrey A Verona, MD
      • Sub-Investigator: Jamie D Trifalgar-Arches, MD
      • Sub-Investigator: Nathaniel Lee, MD
    • Quezon City, National Capital Region, Philippines, 1100
      • Recruiting
      • National Kidney and Transplant Institute
      • Contact: Romina A Danguilan, MD; Phone Number: 1004 (63)(02)8981-0300; Email: radanguilan@gmail.com
      • Principal Investigator: Romina A Danguilan, MD
      • Sub-Investigator: Mel-hatra I Arakama, MD
      • Sub-Investigator: Joselito R Chavez, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Biological: Prophylactic Plasma Transfusion; 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: PPT; Prophylactic Plasma Component Transfusion; Plasma Transfusion; Prophylactic Plasma Component Therapy; Device: Extracorporeal Membrane Oxygenation; 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: Mean blood pressure of >60 mm; SaO2 at >90% with a flow of 3.5-4.5 L/min; Hematocrit at >35%; Platelets >50000-100000/mL; Transfusions will be done when necessary Criteria for weaning: ABG:pH 7.35-7.45PaO2 >80 mm HgPCO2 <45 mm Hg; Under the following conditions:Gas blender FiO2 of 0.21Sweep gas of 0 L/min at an ECMO flow of 2 L/minVentilator mode (if applicable):FiO2 of 0.6Tidal volume of 6 mL/kgPEEP of 8 cmH2ORR of 12-16/min for VV ECMO or 3 L/min of O2 via nasal prong with awakening ECMO patients; Other Names: ECMO; Other: Conventional therapy; 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
Active Comparator: 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).	Device: Extracorporeal Membrane Oxygenation; 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: Mean blood pressure of >60 mm; SaO2 at >90% with a flow of 3.5-4.5 L/min; Hematocrit at >35%; Platelets >50000-100000/mL; Transfusions will be done when necessary Criteria for weaning: ABG:pH 7.35-7.45PaO2 >80 mm HgPCO2 <45 mm Hg; Under the following conditions:Gas blender FiO2 of 0.21Sweep gas of 0 L/min at an ECMO flow of 2 L/minVentilator mode (if applicable):FiO2 of 0.6Tidal volume of 6 mL/kgPEEP of 8 cmH2ORR of 12-16/min for VV ECMO or 3 L/min of O2 via nasal prong with awakening ECMO patients; Other Names: ECMO; Other: Conventional therapy; 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
Experimental: 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.	Device: Extracorporeal Membrane Oxygenation; 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: Mean blood pressure of >60 mm; SaO2 at >90% with a flow of 3.5-4.5 L/min; Hematocrit at >35%; Platelets >50000-100000/mL; Transfusions will be done when necessary Criteria for weaning: ABG:pH 7.35-7.45PaO2 >80 mm HgPCO2 <45 mm Hg; Under the following conditions:Gas blender FiO2 of 0.21Sweep gas of 0 L/min at an ECMO flow of 2 L/minVentilator mode (if applicable):FiO2 of 0.6Tidal volume of 6 mL/kgPEEP of 8 cmH2ORR of 12-16/min for VV ECMO or 3 L/min of O2 via nasal prong with awakening ECMO patients; Other Names: ECMO; Other: Conventional therapy; 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; Device: Hemoperfusion; 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
Active Comparator: 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.	Device: Extracorporeal Membrane Oxygenation; 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: Mean blood pressure of >60 mm; SaO2 at >90% with a flow of 3.5-4.5 L/min; Hematocrit at >35%; Platelets >50000-100000/mL; Transfusions will be done when necessary Criteria for weaning: ABG:pH 7.35-7.45PaO2 >80 mm HgPCO2 <45 mm Hg; Under the following conditions:Gas blender FiO2 of 0.21Sweep gas of 0 L/min at an ECMO flow of 2 L/minVentilator mode (if applicable):FiO2 of 0.6Tidal volume of 6 mL/kgPEEP of 8 cmH2ORR of 12-16/min for VV ECMO or 3 L/min of O2 via nasal prong with awakening ECMO patients; Other Names: ECMO; Other: Conventional therapy; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of CFI levels via qPCR and via ELISA	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.	At baseline and Day 1 post-treatment, assessed up to study completion, an average of 3 years
Hospital Days	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.	From admission to discharge from the hospital, assessed up to study completion, an average of 3 years
Occurrence of Mortality	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.	From admission to discharge from the hospital or date of death, assessed up to study completion, an average of 3 years
Presence of Significant Pulmonary Involvement	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.	From admission to discharge from the hospital, assessed up to study completion, an average of 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need for Renal Replacement Therapy	Number of days requiring dialysis during hospital stay.	From admission to discharge from the hospital, assessed up to study completion, an average of 3 years
Need for Inotropic Support	Number of days requiring inotropic support to attain MAP >65 and number of days requiring each inotrope	From admission to discharge from the hospital, assessed up to study completion, an average of 3 years
Need for Emergent Invasive Respiratory Support	Inability to maintain Sp02 >92% on maximum non-invasive respiratory support	From admission to discharge from the hospital, assessed up to study completion, an average of 3 years
Presence of Refractory Hypotension	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	From admission to discharge from the hospital, assessed up to study completion, an average of 3 years
Presence of Significant Renal Involvement	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.	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	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.	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)	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.	From admission to discharge from the hospital, assessed up to study completion, an average of 3 years
Intensive Care Unit (ICU) Days	Number of days patient is required to stay in ICU (date out of ICU will be date ordered by the attending physician)	From admission into ICU to date out of ICU, assessed up to study completion, an average of 3 years

Collaborators and Investigators

• Sponsor: National Kidney and Transplant Institute, Philippines
• Collaborators: San Lazaro Hospital, Philippines; Institute of Human Genetics, National Institutes of Health - University of the Philippines Manila, Philippines; Department of Science and Technology, Philippines
• Investigators: Principal Investigator: Romina A Danguilan, MD, National Kidney and Transplant Institute, Philippines

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: July 16, 2025
• First Submitted That Met QC Criteria: August 13, 2025
• First Posted (Actual): August 17, 2025

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: complications; extracorporeal membrane oxygenation; CFI; pulmonary complications; hemoperfusion; leptospirosis; plasma transfusion; complement factor I; renal complications
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Spirochaetales Infections; Leptospirosis; Health Services Administration; Health Care Quality, Access, and Evaluation; Therapeutics; Surgical Procedures, Operative; Quality of Health Care; Quality Indicators, Health Care; Respiratory Therapy; Sorption Detoxification; Extracorporeal Circulation; Renal Replacement Therapy; Standard of Care; Extracorporeal Membrane Oxygenation; Hemoperfusion
• Other Study ID Numbers: SJREB 2024-70

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The patient information will not be shared at present as the study is still ongoing and there is intellectual property involved. However, general IPD, such as age, sex, and affliction, will be shared, together with important clinical outcomes such as mortality and incidence of renal and or pulmonary complications, only after appropriate intellectual property protection.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No