Phase II randomized, double blind, placebo controlled, clinical trial of safety and immunogenicity of an inactivated SARS-CoV-2 vaccine FAKHRAVAC in adults aged 18-70 years.

BACKGROUND: The FAKHRAVAC®, an inactivated SARS-CoV-2 vaccine, was assessed for safety and immunogenicity in a phase II trial. METHODS: We did a phase II, single-centered, randomized, double-blind, placebo-controlled clinical trial of the FAKHRAVAC inactivated SARS-CoV-2 vaccine on adults aged 18 to 70. The two parallel groups received two intramuscular injections of either a 10-µg vaccine or a placebo at 2-week intervals. The participants' immunogenicity responses and the occurrence of solicited and unsolicited adverse events were compared over the study period of up to 6 months. Immunogenicity outcomes include serum neutralizing antibody activity and specific IgG antibody levels. RESULTS: Five hundred eligible participants were randomly (1:1) assigned to vaccine or placebo groups. The median age of the participants was 36 years, and 75% were male. The most frequent local adverse reaction was tenderness (21.29% after the first dose and 8.52% after the second dose), and the most frequent systemic adverse reaction was headache (11.24% after the first dose and 8.94% after the second dose). Neutralizing antibody titers two and four weeks after the second injection in the vaccine group showed about 3 and 6 times increase compared to the placebo group (GMR = 2.69, 95% CI 2.32-3.12, N:309) and (GMR = 5.51, 95% CI 3.94-8.35, N:285). A four-fold increase in the neutralizing antibody titer was seen in 69.6% and 73.4% of the participants in the vaccine group two and four weeks after the second dose, respectively. Specific ELIZA antibody response against a combination of S1 and RBD antigens 4 weeks after the second injection increased more than three times in the vaccine compared to the placebo group (GMR = 3.34, 95% CI 2.5-4.47, N:142). CONCLUSIONS: FAKHRAVAC® is safe and induces a significant humoral immune response to the SARS-CoV-2 virus at 10-µg antigen dose in adults aged 18-70. A phase III trial is needed to assess the clinical efficacy. TRIAL REGISTRATION: Trial Registry Number: Ref., IRCT20210206050259N2 ( http://irct.ir ; registered on 08/06/2021).

Anesthesia Management for the Patient with Chronic Decompensated Heart Failure and Low Cardiac Output Undergoing CABG with Advanced Cardiac Monitoring: A Case Report.

Introduction: Heart failure (HF) is a complex clinical syndrome caused by a structural or functional heart disorder. One of the most important challenges for anesthesiologists is the management of anesthesia in patients with severe heart failure, which has been facilitated by advanced monitoring systems. Case Presentation: The patient was a 42-year-old man with a history of hypertension (HTN) and HF with involvement of the three coronary arteries (3VD) with ejection fraction (EF) 15%. He was also a candidate for elective CABG. In addition to the insertion of arterial line in the left radial artery and the Swan-Ganz catheter in the pulmonary artery, the patient was also monitored by the Edwards Lifesciences Vigilance II for cardiac index (CI) and intravenous mixed blood oxygenation (ScvO2). Hemodynamic changes during and after surgery, as well as during inotrope infusion, were controlled, and the amount of fluid therapy was calculated by gold direct therapy (GDT) method. Conclusions: Using PA catheter with advanced monitoring and GDT-based fluid therapy guaranteed a safe anesthesia in this patient with severe heart failure and EF < 20%. Moreover, the postoperative complications and duration of ICU stays were significantly reduced.

Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine (FAKHRAVAC®) in healthy adults aged 18-55 years: Randomized, double-blind, placebo-controlled, phase I clinical trial.

Background: The FAKHRAVAC®, an inactivated SARS-CoV-2 vaccine, was assessed for safety and immunogenicity. Methods and findings: In this double-blind, placebo-controlled, phase I trial, we randomly assigned 135 healthy adults between 18 and 55 to receive vaccine strengths of 5 or 10 µg/dose or placebo (adjuvant only) in 0-14 or 0-21 schedules. This trial was conducted in a single center in a community setting. The safety outcomes in this study were reactogenicity, local and systemic adverse reactions, abnormal laboratory findings, and Medically Attended Adverse Events (MAAE). Immunogenicity outcomes include serum neutralizing antibody activity and specific IgG antibody levels.The most frequent local adverse reaction was tenderness (28.9%), and the most frequent systemic adverse reaction was headache (9.6%). All adverse reactions were mild, occurred at a similar incidence in all six groups, and were resolved within a few days. In the 10-µg/dose vaccine group, the geometric mean ratio for neutralizing antibody titers at two weeks after the second injection compared to the placebo group was 9.03 (95% CI: 3.89-20.95) in the 0-14 schedule and 11.77 (95% CI: 2.77-49.94) in the 0-21 schedule. The corresponding figures for the 5-µg/dose group were 2.74 (1.2-6.28) and 5.2 (1.63-16.55). The highest seroconversion rate (four-fold increase) was related to the 10-µg/dose group (71% and 67% in the 0-14 and 0-21 schedules, respectively). Conclusions: FAKHRAVAC® is safe and induces a strong humoral immune response to the SARS-CoV-2 virus at 10-µg/dose vaccine strength in adults aged 18-55. This vaccine strength was used for further assessment in the phase II trial.Trial registrationThis study is registered with https://www.irct.ir; IRCT20210206050259N1.

Assessment of LV diastolic dysfunction in myocardial perfusion imaging: a correlative study with transthoracic echocardiography.

OBJECTIVE: Myocardial perfusion imaging (MPI) by gated single-photon emission computed tomography (SPECT) is a feasible method in the evaluation of left ventricular perfusion and function. The purpose of this study was to determine the threshold and grading of left ventricular (LV) diastolic dysfunction (LVDD) using gated SPECT MPI. METHODS: A total of 149 patients were recruited in the study. All of the patients underwent a standard 2-day stress/rest gated MPI study and transthoracic echocardiography within 2 weeks. The reconstructed rest-only images were analyzed by Cedar-Sinai's quantitative gated SPECT and the LV diastolic parameters, including peak filling rate (PFR), time to PFR (TTPF) and secondary PFR (PFR2) to PFR ratio were provided and compared to echocardiographic data. RESULTS: 68 (45.6%) and 81 (54.4%) of patients were categorized in LVDD-absent and LVDD-present groups on the basis of LVDD evidence in echocardiography, respectively. receiver-operating-characteristic analysis for PFR and TTPF was performed, resulting in diagnostic sensitivities of 70 and 57% and specificities of 60 and 75% for PFR <2.6 end-diastolic volumes (EDV)/s and TTPF>160.5 ms, respectively. Applying our previously used thresholds of <1.70 EDV/s for PFR, >208 ms for TTPF and >1 for PFR2/PFR, sensitivities and specificities of 9.9 and 96.6%, 9.9 and 95.6% and 13.8 and 88% were resulted, respectively. Grading of LVDD on the basis of MPI-obtained diastolic parameters showed considerable overlapping data by interquartile range. CONCLUSION: Gated SPECT MPI can be used as a highly specific means for detection of LV diastolic dysfunction when compared to echocardiography. However, grading of severity of diastolic heart failure appears to be impracticable.