LeptospirosisPhase 2NCT07127718
Preventive Strategies for Early and Late Complications of Leptospirosis
A Phase 2 study testing Prophylactic Plasma Transfusion, Hemoperfusion and Extracorporeal Membrane Oxygenation in people with Leptospirosis, run by National Kidney and Transplant Institute, Philippines at 3 sites in Philippines.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Leptospirosis
- What is being tested?
- Prophylactic Plasma Transfusion, Hemoperfusion and Extracorporeal Membrane Oxygenation
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 678 participants
- Where
- 3 sitesPhilippines
- Study dates
- 12 Apr 2024to Mar 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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 locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Philippines3 sites, 2 recruiting
- Active, not recruiting
Institute of Human Genetics, National Institutes of Health - University of the Philippines Manila
Manila, National Capital Region, 1000
- Recruiting
San Lazaro Hospital
Manila, National Capital Region, 1003
Rontgene M Solante, MD, (63)(02)5309-9608, rontgenesolante@gmail.com
Rontgene M Solante, MD
- Recruiting
National Kidney and Transplant Institute
Quezon City, National Capital Region, 1100
Romina A Danguilan, MD, (63)(02)8981-0300 ext. 1004, radanguilan@gmail.com
Romina A Danguilan, MD
About this study
Official title: 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?
Read more
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
Read the 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
- Being tested
- Prophylactic Plasma Transfusion, Hemoperfusion, Extracorporeal Membrane Oxygenation, Conventional therapy
- Keywords
- leptospirosis, plasma transfusion, hemoperfusion, extracorporeal membrane oxygenation, complement factor I, CFI, complications, renal complications, pulmonary complications
- Medical subject headings
- Leptospirosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prophylactic Plasma TransfusionBiological
Also called Prophylactic Plasma Component Transfusion, Plasma Transfusion, Prophylactic Plasma Component Therapy, PPT
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.
HemoperfusionDevice
Also called HP
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.
Extracorporeal Membrane OxygenationDevice
Also called ECMO
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
Conventional therapyOther
Also called Standard of care
Conventional therapy for leptospirosis includes antibiotics, fluids, inotropes, renal replacement therapy, ventilator support, and other treatment that the attending physician deems necessary.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: 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. Receives: 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. Receives: Device: Extracorporeal Membrane Oxygenation; Other: Conventional therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Number of days requiring dialysis during hospital stay.
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
Measured: From admission into ICU to date out of ICU, assessed up to study completion, an average of 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2025
- Study start12 Apr 2024
- Primary completionMar 2027 (estimated)
- Study completionMar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (68)Papers the sponsor has linked to this study.
- Other trials for LeptospirosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 678 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Kidney and Transplant Institute, Philippines
- Sponsor type
- University, hospital or other
- 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
- Responsible party
- Principal investigator, Romina A. Danguilan, National Kidney and Transplant Institute, Philippines
- Investigators
- Romina A Danguilan, MD, Principal investigator, National Kidney and Transplant Institute, Philippines
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07127718
- Sponsor's protocol ID
- SJREB 2024-70
- Status last verified
- Apr 2026
- First submitted
- 16 Jul 2025
- Last updated
- 13 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Milhem MM, Knutson T, Yang S, Zhu D, Wang X, Leslie KK, Meng X. Correlation of MTDH/AEG-1 and HOTAIR Expression with Metastasis and Response to Treatment in Sarcoma Patients. J Cancer Sci Ther. 2011 Dec 29;S5(4):004.
PubMed 23543869Popugaev KA, Bakharev SA, Kiselev KV, Samoylov AS, Kruglykov NM, Abudeev SA, Zhuravel SV, Shabanov AK, Mueller T, Mayer SA, Petrikov SS. Clinical and pathophysiologic aspects of ECMO-associated hemorrhagic complications. PLoS One. 2020 Oct 13;15(10):e0240117. doi: 10.1371/journal.pone.0240117. eCollection 2020.
PubMed 33048966Na SJ, Chung CR, Choi HJ, Cho YH, Sung K, Yang JH, Suh GY, Jeon K. The effect of multidisciplinary extracorporeal membrane oxygenation team on clinical outcomes in patients with severe acute respiratory failure. Ann Intensive Care. 2018 Feb 27;8(1):31. doi: 10.1186/s13613-018-0375-9.
PubMed 29484504Combes A, Brodie D, Bartlett R, Brochard L, Brower R, Conrad S, De Backer D, Fan E, Ferguson N, Fortenberry J, Fraser J, Gattinoni L, Lynch W, MacLaren G, Mercat A, Mueller T, Ogino M, Peek G, Pellegrino V, Pesenti A, Ranieri M, Slutsky A, Vuylsteke A; International ECMO Network (ECMONet). Position paper for the organization of extracorporeal membrane oxygenation programs for acute respiratory failure in adult patients. Am J Respir Crit Care Med. 2014 Sep 1;190(5):488-96. doi: 10.1164/rccm.201404-0630CP.
PubMed 25062496Cheng R, Hachamovitch R, Kittleson M, Patel J, Arabia F, Moriguchi J, Esmailian F, Azarbal B. Complications of extracorporeal membrane oxygenation for treatment of cardiogenic shock and cardiac arrest: a meta-analysis of 1,866 adult patients. Ann Thorac Surg. 2014 Feb;97(2):610-6. doi: 10.1016/j.athoracsur.2013.09.008. Epub 2013 Nov 8.
PubMed 24210621Khalid N, Javed H, Ahmad SA, Edelman JJ, Shlofmitz E, Chen Y, Musallam A, Rogers T, Hashim H, Bernardo NL, Waksman R. Analysis of the Food and Drug Administration Manufacturer and User Facility Device Experience Database for Patient- and Circuit-Related Adverse Events Involving Extracorporeal Membrane Oxygenation. Cardiovasc Revasc Med. 2020 Feb;21(2):230-234. doi: 10.1016/j.carrev.2019.11.011. Epub 2019 Nov 20.
PubMed 31767523Xu L, Wu X, Zou Y. Clinical efficacy comparison of HA280 and DNA280 immunoadsorption column in treating systemic lupus erythematosus. Mod Rheumatol. 2016;26(1):94-8. doi: 10.3109/14397595.2015.1056955. Epub 2015 Aug 19.
PubMed 26025438Pomare Montin D, Ankawi G, Lorenzin A, Neri M, Caprara C, Ronco C. Biocompatibility and Cytotoxic Evaluation of New Sorbent Cartridges for Blood Hemoperfusion. Blood Purif. 2018;46(3):187-195. doi: 10.1159/000489921. Epub 2018 Jun 8.
PubMed 29886501Semple JW, Rebetz J, Kapur R. Transfusion-associated circulatory overload and transfusion-related acute lung injury. Blood. 2019 Apr 25;133(17):1840-1853. doi: 10.1182/blood-2018-10-860809. Epub 2019 Feb 26.
PubMed 30808638Vlaar AP, Juffermans NP. Transfusion-related acute lung injury: a clinical review. Lancet. 2013 Sep 14;382(9896):984-94. doi: 10.1016/S0140-6736(12)62197-7. Epub 2013 May 1.
PubMed 23642914Popovsky MA. Transfusion-associated circulatory overload: the plot thickens. Transfusion. 2009 Jan;49(1):2-4. doi: 10.1111/j.1537-2995.2008.02010.x. No abstract available.
PubMed 19140808Chowdary P, Saayman AG, Paulus U, Findlay GP, Collins PW. Efficacy of standard dose and 30 ml/kg fresh frozen plasma in correcting laboratory parameters of haemostasis in critically ill patients. Br J Haematol. 2004 Apr;125(1):69-73. doi: 10.1111/j.1365-2141.2004.04868.x.
PubMed 15015971Alam A, Lin Y, Lima A, Hansen M, Callum JL. The prevention of transfusion-associated circulatory overload. Transfus Med Rev. 2013 Apr;27(2):105-12. doi: 10.1016/j.tmrv.2013.02.001. Epub 2013 Mar 1.
PubMed 23465703Arokianathan D, Trower K, Pooboni S, Sosnowski A, Moss P, Thaker H. Leptospirosis: a case report of a patient with pulmonary haemorrhage successfully managed with extra corporeal membrane oxygenation. J Infect. 2005 Feb;50(2):158-62. doi: 10.1016/j.jinf.2004.09.010.
PubMed 15667919Kahn JM, Muller HM, Kulier A, Keusch-Preininger A, Tscheliessnigg KH. Veno-arterial extracorporeal membrane oxygenation in acute respiratory distress syndrome caused by leptospire sepsis. Anesth Analg. 2006 May;102(5):1597-8. doi: 10.1213/01.ANE.0000215121.67833.2F. No abstract available.
PubMed 16632865