Preventive Strategies for Early and Late Complications of Leptospirosis

National Kidney and Transplant Institute, Philippines

Status and phase: Enrolling; Phase 2

Conditions: Leptospirosis

Treatments: Device: Hemoperfusion; Other: Conventional therapy; Biological: Prophylactic Plasma Transfusion; Device: Extracorporeal Membrane Oxygenation

Study type: Interventional

Funder types: Other

Identifiers

NCT07127718

SJREB 2024-70

Details and patient eligibility

About

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

Full 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.

Enrollment: 678 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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 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 <8 at present. Participant has had chest compressions or CPR
• Pregnancy
• PPTTRT/PPTCONV: Requiring emergent dialyses
• PPTTRT/PPTCONV: Significant renal impairment as defined by eGFR less than 30
• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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678 participants in 4 patient groups

Prophylactic Plasma Component Therapy with Conventional Treatment (PPTTRT)

Experimental group

Description:

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).

Treatment:

Device: Extracorporeal Membrane Oxygenation

Biological: Prophylactic Plasma Transfusion

Other: Conventional therapy

Conventional Treatment (PPTCONV)

Active Comparator group

Description:

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).

Treatment:

Device: Extracorporeal Membrane Oxygenation

Other: Conventional therapy

Hemoperfusion Treatment with Conventional Treatment (HPTRT)

Experimental group

Description:

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.

Treatment:

Device: Extracorporeal Membrane Oxygenation

Other: Conventional therapy

Device: Hemoperfusion

Conventional Treatment (HPCONV)

Active Comparator group

Description:

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.

Treatment:

Device: Extracorporeal Membrane Oxygenation

Other: Conventional therapy