Evaluate the Efficacy and Safety of Various Treatment Schemes for Severe Fever With Thrombocytopenia Syndrome(SFTS)

Study Overview
=================
Brief Summary
-----------------
This is a prospective, multicenter, non-randomized, controlled intervention clinical study.Patients with severe fever with thrombocytopenia syndrome who have been clinically diagnosed and met the study inclusion criteria will be included in the study for analysis. All patients with SFTS will be assigned to different groups according to the ratio of 1:3, including the non-intervention group (conventional treatment group) and the related drug intervention group. Non-intervention group:patients received conventional treatment during hospitalization. Intervention group: Part A group: Patients received methylprednisolone 1-2mg/kg/d（or other glucocorticoid equivalent to methylprednisolone 1-2mg/kg/d) + intravenous immunoglobulin (IVIG) 0.2g-0.4g/kg/d for a total of 3-5 days. If the disease progressed after treatment, the patients was given the dose of rescue therapy (methylprednisolone > 2mg/kg/d or other glucocorticoid equivalent to methylprednisolone > 2mg/kg/d + IVIG 0.4g/kg/d) for another 3-5 days. Part B group: Patients received tocilizumab 4mg/kg once. Part C group: Patients received low molecular weight heparin 100U/kg, qd or q12h IH for 4-7 days. If the platelet count is less than 30 × 10^9/L, the low molecular weight heparin should be discontinued. All patients received conventional treatment. All patients were followed up from the end of treatment to day 28 after completion of treatment.

Official Title
-----------------
Evaluate the Efficacy and Safety of Various Treatment Schemes for Severe Fever With Thrombocytopenia Syndrome：a Prospective, Multicenter, Non-randomized Controlled Intervention Study

Conditions
-----------------
Severe Fever With Thrombocytopenia Syndrome

Intervention / Treatment
-----------------
* Drug: Methylprednisolone
* Drug: intravenous immunoglobulin
* Drug: Tocilizumab
* Drug: Low molecular weight heparin
* Other: conventional treatment


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Age ≥18 years. 2. SFTS Patients met the following diagnostic criteria:SFTS-virus (SFTSV) positive in peripheral blood detected by RT-PCR or Next Generation Sequencing (NGS) . 3. The intervention group shall meet the following conditions: Part A: Treatment can be initiated if the patient has two of the following conditions: (1) Persistent high fever for 7 days or more; (2) Platelets less than 50×10^9/L; (3) Multiple organ function impairment (MODS) including brain, heart, liver, kidney and blood coagulation; (4) Failure of more than 1 organ, such as brain, heart, liver, kidney and coagulation. Part B: Serum cytokine IL-6 quantification >2 times the upper limit of normal (ULN). Part C: Plasma D-D dimer ≥ 4×ULN. 4. Sign written informed consent and cooperate with follow-up. Exclusion Criteria: Patients with neoplastic diseases. Patients with severe chronic diseases, such as chronic kidney disease stage 3-5, chronic heart failure, decompensated cirrhosis, chronic diseases of the central nervous system, hematologic neoplastic diseases, uncontrolled solid tumors, etc. Patients who are or may be pregnant. Patients with a history of hypersensitivity reaction to the trial drug and its components. Patients with conditions that the investigator judged to affect short-term survival. Additional exclusion criteria for Part B: Patients with platelet < 50×10^9/L Additional exclusion criteria for Part C: Received vasopressor therapy for more than 36 hours before enrollment; Indications for anticoagulant therapy (such as ACS, acute VTE, mechanical valve, etc.); Significant bleeding risk as evidenced by one of the following conditions: Clinical: Surgery that requires general or spinal anesthesia within 24 hours prior to enrollment, or may require such surgery within the next 24 hours; Evidence of active bleeding; A history of severe head trauma requiring hospitalization; History of intracranial surgery or stroke or any cerebral arteriovenous malformation, cerebral aneurysm, or central nervous system mass within 3 months prior to the study; History of congenital hemorrhage; Gastrointestinal bleeding occurred within 6 weeks before the study unless corrective surgery was performed; Trauma that is thought to increase the risk of bleeding; The presence of an epidural catheter; Laboratory: INR > 2.0, or thrombelastogram results suggest significant hyperfibrinolysis. Present with other forms of shock that are clinically apparent, including cardiogenic, obstructive (massive pulmonary embolism, cardiac tamponade, tension pneumothorax), hemorrhagic, neurogenic, or anaphylactic shock.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: non-intervening group<br>conventional treatment，including symptomatic and supportive treatment, antiviral treatment etc. | Other: conventional treatment<br>* conventional treatment，including symptomatic and supportive treatment, antiviral treatment etc.<br>|
| Experimental: intervention group<br>Part A group: Patients received methylprednisolone 1-2mg/kg/d（or other glucocorticoid equivalent to methylprednisolone 1-2mg/kg/d) + IVIG 0.2g-0.4g/kg/d for a total of 3-5 days. If the disease progressed after treatment, the patients were given the dose of rescue therapy (methylprednisolone > 2mg/kg/d or other glucocorticoid equivalent to methylprednisolone > 2mg/kg/d + IVIG 0.4g/kg/d) for another 3-5 days. Part B group: Patients received tocilizumab 4mg/kg once. Part C group: Patients received low molecular weight heparin 100U/kg, qd or q12h IH for 4-7 days. All patients received conventional treatment. All patients were followed up from the end of treatment to day 28 after completion of treatment. | Drug: Methylprednisolone<br>* Methylprednisolone:1-2mg/kg/d(or other glucocorticoid equivalent to methylprednisolone 1-2mg/kg/d),ivgtt,3-5 days.If disease progression occurs after completion of treatment, the dose of salvage therapy (methylprednisolone > 2mg/kg/d or other glucocorticoid equivalent to methylprednisolone > 2mg/kg/d) was continued for another 3-5 days.<br>Drug: intravenous immunoglobulin<br>* intravenous immunoglobulin:0.2g-0.4g/kg/d,ivgtt, 3-5 days.If disease progression occurs after completion of treatment, the dose of salvage therapy (IVIG 0.4g/kg/d) was continued for another 3-5 days.<br>Drug: Tocilizumab<br>* Tocilizumab:4mg/kg, once<br>Drug: Low molecular weight heparin<br>* Low molecular weight heparin:100U/kg, qd or q 12h,IH,4-7 days<br>Other: conventional treatment<br>* conventional treatment，including symptomatic and supportive treatment, antiviral treatment etc.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28-day survival rate | 28-day survival rate was defined as the proportion of patients who were still alive 28 days after enrollment. | From enrollment to 28 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of complications | The complications include Respiratory system, gastrointestinal system, blood system, nervous system, liver and kidney, lymphatic system, multiple organ dysfunction syndrome may be related to Severe Fever With Thrombocytopenia Syndrome.Incidence of complications was defined as the proportion of complications occur after enrollment. | From enrollment to 28 day | 
| Incidence of AEs | Incidence of adverse events associated with trial drug treatment: blood glucose, electrolyte disturbances, osteoporosis, Cushing's syndrome, double infection, active bleeding, etc. | From enrollment to 28 day | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
interleukin-6, D-D dimer, efficacy, safety, severe SFTS