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

Sponsor

Qin Ning (Other)

Overall Status

Recruiting

CT.gov ID

NCT05604859

Collaborator

(none)

350

Enrollment

Locations

Arms

22.4

Anticipated Duration (Months)

Patients Per Site

1.6

Patients Per Site Per Month

Study Details

Study Description

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 standard care during hospitalization.

Intervention group:

Part A group: Patients received methylprednisolone 2mg/kg/d + intravenous immunoglobulin (IVIG) 20g/d for a total of 5 days. If the disease progressed after treatment, the patients was given the dose of rescue therapy (methylprednisolone > 2mg/kg/d + IVIG 20g/d) for another 5 days.

Part B group: Patients received tocilizumab 4mg/kg once. Part C group: Patients received low molecular weight heparin 100U/kg, q12h IH for 7 days.

All patients were followed up from the end of treatment to day 28 after completion of treatment.

Condition or Disease	Intervention/Treatment	Phase
Severe Fever With Thrombocytopenia Syndrome	Drug: Methylprednisolone Drug: intravenous immunoglobulin Drug: Tocilizumab Drug: Low molecular weight heparin Other: standard treatment	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

350 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

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

Actual Study Start Date :

Aug 19, 2022

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Jun 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: non-intervening group Standard treatment plan	Other: standard treatment Conventional therapy:symptomatic treatment,includes reducing fever and ensuring water, electrolyte and acid-base balance,etc.
Experimental: intervention group Part A group: Patients received methylprednisolone 2mg/kg/d + IVIG 20g/d for a total of 5 days. If the disease progressed after treatment, the patients were given the dose of rescue therapy (methylprednisolone > 2mg/kg/d + IVIG 20g/d) for another 5 days. Part B group: Patients received tocilizumab 4mg/kg once. Part C group: Patients received low molecular weight heparin 100U/kg, q12h IH for 7 days. All patients were followed up from the end of treatment to day 28 after completion of treatment.	Drug: Methylprednisolone Methylprednisolone:2mg/kg/d,ivgtt,day 1- 5.If disease progression occurs after completion of treatment, the dose of salvage therapy (methylprednisolone > 2mg/kg/d) was continued for another 5 days. Drug: intravenous immunoglobulin intravenous immunoglobulin:20g/d,ivgtt,day 1-5.If disease progression occurs after completion of treatment, the dose of salvage therapy (IVIG 20g/d) was continued for another 5 days. Drug: Tocilizumab Tocilizumab:4mg/kg,day 1. Drug: Low molecular weight heparin Low molecular weight heparin:100U/kg,q 12h,IH,day 1-7. Other: standard treatment Conventional therapy:symptomatic treatment,includes reducing fever and ensuring water, electrolyte and acid-base balance,etc.

Arm

Intervention/Treatment

Active Comparator: non-intervening group

Standard treatment plan

Other: standard treatment

Conventional therapy:symptomatic treatment,includes reducing fever and ensuring water, electrolyte and acid-base balance,etc.

Experimental: intervention group

Part A group: Patients received methylprednisolone 2mg/kg/d + IVIG 20g/d for a total of 5 days. If the disease progressed after treatment, the patients were given the dose of rescue therapy (methylprednisolone > 2mg/kg/d + IVIG 20g/d) for another 5 days. Part B group: Patients received tocilizumab 4mg/kg once. Part C group: Patients received low molecular weight heparin 100U/kg, q12h IH for 7 days. All patients were followed up from the end of treatment to day 28 after completion of treatment.

Drug: Methylprednisolone

Methylprednisolone:2mg/kg/d,ivgtt,day 1- 5.If disease progression occurs after completion of treatment, the dose of salvage therapy (methylprednisolone > 2mg/kg/d) was continued for another 5 days.

Drug: intravenous immunoglobulin

intravenous immunoglobulin:20g/d,ivgtt,day 1-5.If disease progression occurs after completion of treatment, the dose of salvage therapy (IVIG 20g/d) was continued for another 5 days.

Drug: Tocilizumab

Tocilizumab:4mg/kg,day 1.

Drug: Low molecular weight heparin

Low molecular weight heparin:100U/kg,q 12h,IH,day 1-7.

Other: standard treatment

Conventional therapy:symptomatic treatment,includes reducing fever and ensuring water, electrolyte and acid-base balance,etc.

Outcome Measures

Primary Outcome Measures

28-day survival rate [From enrollment to 28 day]
28-day survival rate was defined as the proportion of patients who were still alive 28 days after enrollment.

Secondary Outcome Measures

Incidence of complications [From enrollment to 28 day]
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.
Incidence of AEs [From enrollment to 28 day]
Incidence of adverse events associated with trial drug treatment: blood glucose, electrolyte disturbances, osteoporosis, Cushing's syndrome, double infection, active bleeding, etc.

Other Outcome Measures

Biomarkers associated with efficacy [From enrollment to 12 month]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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) .
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.

Contacts and Locations

Locations

	Site	City	State	Country
1	Guangshui First Peoples Hospital	Guangshui	Hubei	China
2	Huanggang Central Hospital	Huanggang	Hubei	China
3	Luotian County Peoples Hospital	Huanggang	Hubei	China
4	Macheng Peoples Hospital	Macheng	Hubei	China
5	Qianjiang Central Hospital	Qianjiang	Hubei	China
6	Suizhou Central Hospital	Suizhou	Hubei	China
7	Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei	China
8	Xianning Central Hospital	Xianning	Hubei	China
9	Yichang Third Peoples Hospital	Yichang	Hubei	China
10	Jiangsu Province Hospital	Nanjing	Jiangsu	China