Preventive Strategies for Early and Late Complications of Leptospirosis
ConditionLeptospirosis
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-60
SponsorNational Kidney and Transplant Institute, Philippines
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Prophylactic Plasma Transfusion
Biological/VaccineABO/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.
Hemoperfusion
DeviceThe 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.
Extracorporeal Membrane Oxygenation
DeviceA 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
Conventional therapy
Other interventionConventional therapy for leptospirosis includes antibiotics, fluids, inotropes, renal replacement therapy, ventilator support, and other treatment that the attending physician deems necessary.
Treatment groups
678 Participants
are divided into 4 treatment groupsGroup A: Prophylactic Plasma Component Therapy with Conventional Treatment (PPTTRT)Experimental treatment 3 interventions
Group B: Conventional Treatment (PPTCONV)Active comparator 2 interventions
Group C: Hemoperfusion Treatment with Conventional Treatment (HPTRT)Experimental treatment 3 interventions
Group D: Conventional Treatment (HPCONV)Active comparator 2 interventions
Trial outcomes
Primary outcomes
1
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.
Time frame
At baseline and Day 1 post-treatment, assessed up to study completion, an average of 3 years2
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.
Time frame
From admission to discharge from the hospital, assessed up to study completion, an average of 3 years3
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.
Time frame
From admission to discharge from the hospital or date of death, assessed up to study completion, an average of 3 years4
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.
Time frame
From admission to discharge from the hospital, assessed up to study completion, an average of 3 yearsSecondary outcomes
1
Need for Renal Replacement Therapy
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 years2
Need for Inotropic Support
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 years3
Need for Emergent Invasive Respiratory Support
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 years4
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
Time frame
From admission to discharge from the hospital, assessed up to study completion, an average of 3 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
National Kidney and Transplant Institute, Philippines
Lead sponsor
San Lazaro Hospital, Philippines
Collaborator
Institute of Human Genetics, National Institutes of Health - University of the Philippines Manila, Philippines
Collaborator
Department of Science and Technology, Philippines
Collaborator
Source ClinicalTrials.gov