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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Severe Fever With Thrombocytopenia Syndrome
• Intervention / Treatment: Other: conventional treatment; Drug: Methylprednisolone; Drug: intravenous immunoglobulin; Drug: Tocilizumab; Drug: Low molecular weight heparin

• Study Type: Interventional
• Enrollment (Estimated): 350
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Qin Ning, MD., PhD; Phone Number: +8602783662391; Email: qning@vip.sina.com

Study Locations

• China
  • Hubei
    • Guangshui, Hubei, China
      • Recruiting
      • Guangshui First Peoples Hospital
      • Contact: qian Liu
    • Huanggang, Hubei, China
      • Not yet recruiting
      • Huanggang Central Hospital
      • Contact: guoxiang Zhu
    • Huanggang, Hubei, China
      • Recruiting
      • Luotian County Peoples Hospital
      • Contact: Wei Wang
    • Macheng, Hubei, China
      • Recruiting
      • Macheng Peoples Hospital
      • Contact: Yi Zhou
    • Qianjiang, Hubei, China
      • Not yet recruiting
      • Qianjiang Central Hospital
      • Contact: Jun Wang
    • Suizhou, Hubei, China
      • Recruiting
      • Suizhou Central Hospital
      • Contact: tiantong Zhou
    • Wuhan, Hubei, China
      • Recruiting
      • Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Qin Ning, PHD,MD; Phone Number: +8602783662391; Email: qning@vip.sina.com
      • Principal Investigator: Qin Ning, PHD,MD
      • Sub-Investigator: Tao Chen, PHD,MD
    • Xianning, Hubei, China
      • Not yet recruiting
      • Xianning Central Hospital
      • Contact: jun Zhu
    • Yichang, Hubei, China
      • Not yet recruiting
      • Yichang Third Peoples Hospital
      • Contact: quan Ming
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Not yet recruiting
      • Jiangsu Province Hospital
      • Contact: chuanlong Zhu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

1. 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.
2. Part B: Serum cytokine IL-6 quantification >2 times the upper limit of normal (ULN).
3. Part C: Plasma D-D dimer ≥ 4×ULN. 4. Sign written informed consent and cooperate with follow-up.

Exclusion Criteria:

1. Patients with neoplastic diseases.
2. 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.
3. Patients who are or may be pregnant.
4. Patients with a history of hypersensitivity reaction to the trial drug and its components.
5. 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:

1. Received vasopressor therapy for more than 36 hours before enrollment;
2. Indications for anticoagulant therapy (such as ACS, acute VTE, mechanical valve, etc.);

3. 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.

4. 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: non-intervening group; conventional treatment，including symptomatic and supportive treatment, antiviral treatment etc.	Other: conventional treatment; conventional treatment，including symptomatic and supportive treatment, antiviral treatment etc.
Experimental: intervention group; 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.	Other: conventional treatment; conventional treatment，including symptomatic and supportive treatment, antiviral treatment etc.; Drug: Methylprednisolone; 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.; Drug: intravenous immunoglobulin; 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.; Drug: Tocilizumab; Tocilizumab:4mg/kg, once; Drug: Low molecular weight heparin; Low molecular weight heparin:100U/kg, qd or q 12h,IH,4-7 days

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers associated with efficacy	Blood, bone marrow, lymph node, urine and stool samples were collected to explore biomarkers associated with predicting the efficacy of methylprednisolone combined with IVIG, tocilizumab and low molecular weight heparin in the treatment of severe fever with thrombocytopenia syndrome.	From enrollment to 12 month

Collaborators and Investigators

• Sponsor: Qin Ning
• Investigators: Study Chair: Qin Qin, MD., PhD, Department of Infectious Disease, Tongji Hospital, Tongji Medical College, HUST

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2022
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: October 31, 2022
• First Submitted That Met QC Criteria: October 31, 2022
• First Posted (Actual): November 3, 2022

Study Record Updates

• Last Update Posted (Actual): July 21, 2023
• Last Update Submitted That Met QC Criteria: July 19, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: safety; efficacy; interleukin-6; D-D dimer; severe SFTS
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Disease; Hematologic Diseases; Vector Borne Diseases; Blood Platelet Disorders; Body Temperature Changes; Tick-Borne Diseases; Bunyaviridae Infections; Syndrome; Fever; Thrombocytopenia; Severe Fever with Thrombocytopenia Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuroprotective Agents; Protective Agents; Anticoagulants; Methylprednisolone; Immunoglobulins; Immunoglobulins, Intravenous; Heparin; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: UNBRELLA STUDY

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No