NCT07127718

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 678 (estimated)
• Sponsor: National Kidney and Transplant Institute, Philippines · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

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

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.

Conditions

• Leptospirosis

Interventions

Type	Name	Description
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.
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.
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 7.35-7.45 * PaO2 \>80 mm Hg * PCO2 \<45 mm Hg * Under the following conditions: * Gas blender FiO2 of 0.21 * Sweep gas of 0 L/min at an ECMO flow of 2 L/min * Ventilator mode (if applicable): * FiO2 of 0.6 * Tidal volume of 6 mL/kg * PEEP of 8 cmH2O * RR of 12-16/min for VV ECMO or 3 L/min of O2 via nasal prong with awakening ECMO patients
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.

Timeline

• Start date: 2024-04-12
• Primary completion: 2027-03-01
• Completion: 2027-03-01
• First posted: 2025-08-17
• Last updated: 2026-04-13

Locations

3 sites across 1 country: Philippines