Clinical trial NCT06597682: Evaluating Immunomodulatory Interventions in Post-Acute Sequelae of SARS-CoV-2 InfEction
Official title: A Randomized Controlled Basket Study for Evaluating Immunomodulatory Interventions in Post-Acute Sequelae of SARS-CoV-2 InfEction (RISE)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Post-acute Sequelae of SARS-COV-2 Infection
Keywords: Post-acute Sequelae of SARS-COV-2 Infection
Long COVID
Immunomodulatory Interventions
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
First posted: 2024-09-19
Enrollment: 632
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a prospective, randomized controlled, basket trial. Patients diagnosed with Post-Acute Sequelae of SARS-CoV-2 Infection who meet the inclusion and exclusion criteria are recruited and divided into three symptom clusters: Inflammatory Cardiac involvement symptoms cluster, cough symptoms cluster and fatigue symptoms cluster. Each symptom cluster is randomly divided into an experimental group and a control group, Patients who do not accept treatment can be included in the observational cohort. Subjects in the experimental group receive immunomodulatory interventions plus conventional treatment, while subjects in the control group receive conventional treatment only. Subjects in each symptom cluster undergo clinical medical record data collection, laboratory tests, and imaging examinations at specified time points, as well as records of adverse events.


Eligibility criteria: Inclusion Criteria:

* 1. Age ≥18 years;
* 2. Post-infection with SARS-CoV-2 for more than 3 months and meets the World Health Organization (WHO) definition of Long COVID;
* 3. Symptom criteria: Meet the inclusion and exclusion criteria for each symptom cluster;
* 4. Fertile female subjects are not breastfeeding or pregnant at the time of enrollment (negative urine pregnancy test);
* 5. Willing and able to provide informed consent, complete surveys, clinical assessments, and all necessary follow-up visits;

Symptom Cluster Inclusion Criteria:

* Inflammatory Cardiac Involvement Symptom Cluster
* 1) Age: 18-75 years old;
* 2) Presence of cardiac symptoms at the time of enrollment (e.g., Chest tightness after physical activity, chest pain, difficulty breathing, palpitations, fatigue, etc.);
* 3) CMR shows the following abnormal findings based on any of the following criteria:
* a) Native T1 increase ≥ 1130 milliseconds at 3.0 T (or an increase of 1030 milliseconds at 1.5 T) and/or;
* b) Native T2 ≥ 39.5 milliseconds at 3.0 T (or 49.5 milliseconds at 1.5 T) and/or;
* c) Presence of non-ischemic myocardial and pericardial late gadolinium enhancement and/or;
* d) Left ventricular ejection fraction ≥ 40% and ≤50%.
* Cough Symptom Cluster
* 1) Clinical assessment of cough according to ACCP guidelines indicates no cough caused by other diseases such as COPD, asthma, chronic bronchitis, gastroesophageal reflux, bronchiectasis, etc.;
* 2) Chest X-ray or CT scan shows no abnormalities that could lead to cough or other serious lung diseases;
* 3) FENO ≥25 ppb, or the proportion of eosinophils in sputum cytology ≥2.5%; or the blood eosinophil count \>0.3×10⁹/L.
* Fatigue Symptom Cluster
* 1) Fatigue Severity Scale (FSS) average score ≥ 4;
* 2) Any inflammatory marker (CRP, ESR, PCT, ferritin, IL-6, TNFα) is above the upper limit of normal.

Exclusion Criteria:

* 1. Known SARS-CoV-2 infection within 3 months prior to the date of informed consent signature;
* 2. Systemic fungal infection and active infections that cannot be controlled by anti-infective agents;
* 3. Current or recent (within the last 10 weeks) use of glucocorticoids, other immunosuppressants, or biologic agents;
* 4. Known allergy/sensitivity or any hypersensitivity reaction to the study intervention or control components;
* 5. Known contraindications to the study intervention;
* 6. Any persistent central nervous system disorders, psychiatric illnesses, chronic respiratory or cardiac diseases, Underlying diseases (poorly controlled diabetes, poorly controlled hypertension, peripheral edema, cataracts or glaucoma, peptic ulcer disease, femoral head necrosis, low bone density, or osteoporosis);
* 7. For female participants: pregnant or breastfeeding at screening, or expecting to become pregnant during the study period; women of childbearing age who are unwilling to use effective contraceptive measures (defined as PEARL index \<1, such as birth control pills, intrauterine devices);
* 8. Known alcohol, drug, or chemical abuse;
* 9. Currently participating in another clinical trial;
* 10. Deemed ineligible to participate in this study by the investigator's assessment.

Symptom Cluster Exclusion Criteria:

* Inflammatory Cardiac Involvement Symptom Cluster
* 1) Past medical history or cardiac magnetic resonance (CMR) evidence indicating significant cardiac disease, including:
* a) Known left ventricular ejection fraction (LVEF) \<40% indicating cardiac dysfunction;
* b) Congestive heart failure (New York Heart Association Class III-IV);
* c) Ongoing treatment for heart failure (including HFrEF and HFpEF);
* d) Confirmed ischemic heart disease, peripheral artery disease, and/or cerebrovascular disease;
* e) Persistent or permanent atrial fibrillation or significant arrhythmias;
* f) Congenital or clinically relevant valvular heart disease (moderate or severe);
* g) Specific cardio myopathies (hypertrophic, hypertensive heart disease, amyloidosis, previous myocarditis, non-ischemic dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, non-compacted cardiomyopathy, etc.);
* 2) Contraindications for contrast-enhanced cardiac magnetic resonance (CMR) imaging, such as: use of implanted devices not compatible with MRI; known allergy to gadolinium-based contrast agents (CBGA);
* 3) Patients with structural heart disease or incidental arrhythmias detected on cardiac magnetic resonance imaging will be advised to consult their physicians.
* Cough Symptom Cluster
* 1) Current smoker or having quit smoking for less than 6 months;
* 2) Intolerance to pulmonary function testing and/or FeNO;
* 3) Chest CT showing acute pulmonary infection-related diseases;
* 4) Forced expiratory volume in 1 second (FEV1) / Forced vital capacity (FVC) ratio less than 60%;
* 5) Currently taking or having used angiotensin-converting enzyme inhibitors (ACEI) within the past 3 months of screening;
* 6) Received any relevant traditional Chinese or Western medical treatment within the last month.
* Fatigue Symptom Cluster
* 1) Received any relevant traditional Chinese or Western medical treatment within the last month, taking sedatives, hypnotics, melatonin, or antidepressants;
* 2) Known previous diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome unrelated to SARS-CoV-2 infection;
* 3) Known previous autonomic dysfunction unrelated to SARS-CoV-2 infection;
* 4) Fatigue caused by metabolism-related diseases (such as hyperthyroidism or hypothyroidism, malnutrition) that developed following SARS-CoV-2 infection.

Primary outcomes:
measure: Inflammatory Cardiac Involvement symptom cluster: cardiac magnetic resonance (CMR) indicators
timeFrame: 4 weeks
measure: Cough symptom cluster: Leicester Cough Questionnaire (LCQ) scale scores
timeFrame: 8 weeks
measure: Fatigue symptom cluster: Fatigue Severity Scale (FSS) scale scores
timeFrame: 4 weeks
Secondary outcomes:
measure: Inflammatory Cardiac Involvement symptom cluster: other relevant cardiac magnetic resonance (CMR) indicators
timeFrame: 4 weeks
measure: Inflammatory Cardiac Involvement symptom cluster: VO2max
timeFrame: At baseline, 4 weeks
measure: Inflammatory Cardiac Involvement symptom cluster: Kansas City Cardiomyopathy Questionnaire (KCCQ) scores
timeFrame: At baseline, 4, 8, 12, and 24 weeks
measure: Inflammatory Cardiac Involvement symptom cluster: Change in cTNT Levels
timeFrame: At baseline, 4, 8, 12 and 24 weeks
measure: Inflammatory Cardiac Involvement symptom cluster: the proportion of patients experiencing heart failure and major adverse cardiac events (MACE)
timeFrame: From baseline to 52 weeks
measure: EuroQoL 5-Dimension 5-Level (EQ-5D-5L) questionnaire scores
timeFrame: At baseline, 4, 8, 12 and 24 weeks
measure: Pittsburgh Sleep Quality Index (PSQI) scores
timeFrame: At baseline 4, 8, 12, and 24 weeks
measure: Generalized Anxiety Disorder-7 (GAD-7)
timeFrame: At baseline, 4, 8, 12 and 24 weeks
measure: Patient Health Questionnaire-9 (PHQ-9) depression symptom cluster scores
timeFrame: At baseline, 4, 8, 12 and 24 weeks
measure: Cough symptom cluster: Visual Analogue Scale (VAS)
timeFrame: At baseline 4, 8 and 12 weeks
measure: Cough symptom cluster: pulmonary function and fractional exhaled nitric oxide (FeNO) levels
timeFrame: At baseline and 8 weeks
measure: Fatigue symptom cluster: Visual Analogue Scale (VAS)
timeFrame: At baseline, 4, 8, and 12 weeks
measure: Change in proBNP Levels
timeFrame: Baseline, 4, 8, 12, 24 weeks
measure: Change in Angiotensin II Levels
timeFrame: Baseline, 4, 8, 12, 24 weeks
measure: Change in Ferritin Levels
timeFrame: Baseline, 4, 8, 12, 24 weeks
measure: Change in IL-6 Levels
timeFrame: Baseline, 4, 8, 12, 24 weeks
measure: Change in hsCRP Levels
timeFrame: Baseline, 4, 8, 12, 24 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Huashan Hospital of Fudan University
state: Shanghai
Study officials:
References: