Preventive Strategies for Early and Late Complications of Leptospirosis

NCT07127718 | Recruiting Phase 2

• 1 other identifier: SJREB 2024-70
• Study Type: interventional
• Target: 678
• Locations: 1 country
• Sites: 3

Brief 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

Conditions

Leptospirosis

Keywords

leptospirosis; plasma transfusion; hemoperfusion; extracorporeal membrane oxygenation; complement factor I; CFI; complications; renal complications; pulmonary complications

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (8)

• Need for Renal Replacement Therapy

  From admission to discharge from the hospital, assessed up to study completion, an average of 3 years

• Need for Inotropic Support

  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 Refractory Hypotension

  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

Study Arms (4)

Prophylactic Plasma Component Therapy with Conventional Treatment (PPTTRT)

EXPERIMENTAL

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; Device: Extracorporeal Membrane Oxygenation; Other: Conventional therapy

Conventional Treatment (PPTCONV)

ACTIVE COMPARATOR

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; Other: Conventional therapy

Hemoperfusion Treatment with Conventional Treatment (HPTRT)

EXPERIMENTAL

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: Hemoperfusion; Device: Extracorporeal Membrane Oxygenation; Other: Conventional therapy

Conventional Treatment (HPCONV)

ACTIVE COMPARATOR

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; Other: Conventional therapy

Interventions

Hemoperfusion DEVICE

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.

Also known as: HP

Hemoperfusion Treatment with Conventional Treatment (HPTRT)

Prophylactic Plasma Transfusion BIOLOGICAL

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.

Also known as: Prophylactic Plasma Component Transfusion, Plasma Transfusion, Prophylactic Plasma Component Therapy, PPT

Prophylactic Plasma Component Therapy with Conventional Treatment (PPTTRT)

Extracorporeal Membrane Oxygenation DEVICE

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

Also known as: ECMO

Conventional Treatment (HPCONV); Conventional Treatment (PPTCONV); Hemoperfusion Treatment with Conventional Treatment (HPTRT); Prophylactic Plasma Component Therapy with Conventional Treatment (PPTTRT)

Conventional therapy OTHER

Conventional therapy for leptospirosis includes antibiotics, fluids, inotropes, renal replacement therapy, ventilator support, and other treatment that the attending physician deems necessary.

Also known as: Standard of care

Conventional Treatment (HPCONV); Conventional Treatment (PPTCONV); Hemoperfusion Treatment with Conventional Treatment (HPTRT); Prophylactic Plasma Component Therapy with Conventional Treatment (PPTTRT)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Kidney and Transplant Institute, Philippines: lead
• San Lazaro Hospital, Philippines: collaborator
• Department of Science and Technology, Philippines: collaborator
• Institute of Human Genetics, National Institutes of Health - University of the Philippines Manila, Philippines: collaborator

Study Sites (3)

Institute of Human Genetics, National Institutes of Health - University of the Philippines Manila

Manila, National Capital Region, 1000, Philippines

ACTIVE NOT RECRUITING

San Lazaro Hospital

Manila, National Capital Region, 1003, Philippines

RECRUITING

National Kidney and Transplant Institute

Quezon City, National Capital Region, 1100, Philippines

RECRUITING

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MeSH Terms

Conditions

Leptospirosis

Interventions

Hemoperfusion; Extracorporeal Membrane Oxygenation; Standard of Care

Condition Hierarchy (Ancestors)

Spirochaetales Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Renal Replacement Therapy; Therapeutics; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative; Respiratory Therapy; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Romina A Danguilan, MD

  National Kidney and Transplant Institute, Philippines

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Romina Danguilan, MD

CONTACT

(63)(02)8981-0300; radanguilan@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy Executive Director for Medical Services

Study Record Dates

• First Submitted: July 16, 2025
• First Posted: August 17, 2025
• Study Start: April 12, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

PH (3)