The Fleming [FMTVDM] Directed CoVid-19 Treatment Protocol (FMTVDM)

Diagnostic determination of disease and treatment responses has been limited to qualitative imaging, measurement of serum markers of disease, and sampling of tissue. In each of these instances, there is a built in error either due to sensitivity and specificity issues, clinician interpretation of results, or acceptance of the use of an indirect marker (blood test) of what is happening elsewhere in the body - at the tissue level.

The Fleming Method for Tissue and Vascular Differentiation and Metabolism (FMTVDM) using same state single or sequential quantification comparisons [1] provides the first and only patented test (#9566037) - along with the associated submitted patent applications ruled to be covered under #9566037 - that quantitatively measures changes in tissue resulting from inter alia a disease process. This includes inter alia coronary artery disease (CAD), cancer and infectious/inflammatory processes including CoVid-19 pneumonia (CVP) resulting from the metabolic and regional blood flow differences (RBFDs) caused by these diseases.

The purpose of this paper is to make clinicians and researchers aware of this proposed method for investigating the prevalence and severity of CVP - in addition to providing rapid determination of treatment response in each patient, directing treatment decisions; thereby reducing the loss of time, money, resources and patient lives.

Study Overview

• Status: Completed
• Conditions: CoVid 19 Positive
• Intervention / Treatment: Drug: Hydroxychloroquine, Azithromycin; Drug: Hydroxychloroquine, Doxycycline; Drug: Hydroxychloroquine, Clindamycin; Drug: Hydroxychloroquine, Clindamycin, Primaquine - low dose.; Drug: Hydroxychloroquine, Clindamycin, Primaquine - high dose.; Drug: Remdesivir; Drug: Tocilizumab; Drug: Methylprednisolone; Drug: Interferon-Alpha2B; Drug: Losartan; Drug: Convalescent Serum

Detailed Description

FMTVDM - See Appendix A.

1. Quantitatively calibrates the nuclear camera to guarantee that the measurements made by the camera are accurate, consistent and reproducible. This quantification is dependent upon the isotope being used, the camera and the timing sequence of image acquisition. Such calibration is NOT currently done and it is part of the patent. Studies have demonstrated that the lack of this quantitative calibration has resulted in up to 1/3 of the data being lost for SUV and qualitative interpretation; in addition to making quantification impossible.
2. The patient presents in a fasting state - to eliminate digestive processes from interfering with blood flow distributions - and the differences in metabolic and regional blood flow differences (RBFDs) are enhanced with vasodilatory agents, shifting blood flow and isotope towards regions of greater blood flow and metabolism; enhancing isotope delivery, uptake and quantification.

3. With a now quantitatively calibrated nuclear camera - in this instance a PLANAR camera - or SPECT/CT or PET/CT/MRI if specifically approved - to allow imaging to be done at patient's bedside reducing the use of hospital resources required for transport and decrease potential for patient complications resulting from a transport - image acquisition will occur for 10-minutes following peak enhancement effect of the vasodilatory agent and timed injection of the isotope based upon the enhancing agent.

   Regions-of-interest (ROIs) will drawn by the nuclear technologist - either at the bedside or in the nuclear laboratory - to provide FMTVDM measurements using software already present in the nuclear camera systems. Specific ROIs will be drawn of the right lung (total), left lung (total), mediastinum (thymus activity), and any specific areas where increased tracer uptake is noted.

4. These FMTVDM measurements including MAXIMAL COUNTS +/- VARIANCE, provide the values of the most active pulmonary tissue resulting from the CoVid-19 infection and inflammatory response; just as it has previously been used for CAD and Cancer.
5. From these FMTVDM measurements, the pulmonary tissue and the CoVid-19 infectious process results are placed on a Health-Spectrum showing where in the tissue transitioning process the patient is. The measurements also provide information about how rapidly the tissue is changing. FMTVDM provides the quantitative measurement of where the patient is at any point in time during their course of treatment and how they compare with other patients.
6. Once the FMTVDM measurements have been obtained, treatment decisions can be made based upon serial changes in FMTVDM. Treatments outcomes are based upon FMTVDM measurements, including the maximum FMTVDM and the variance in those measurements. By comparing serial FMTVDM results, improvement or deterioration in the patient's health and the success or failure of the current treatment regimen is measured, providing patient-centered, patient-specific, patient-oriented and patient-directed decisions. Thus saving time, money, resources and lives - not to mention unnecessary side effects from treatment, which is not working.

• Study Type: Interventional
• Enrollment (Actual): 1800
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90245
      • FHHI-OI-Camelot; QME

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: CoVid-19 -

Exclusion Criteria: Decision by patient to not participate.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment 1; Hydroxychloroquine 200 mg po q 8 hrs (600 mg qD) for a total of 10-days OR Hydroxychloroquine 155 mg IV every 8-hours (600 mg qD) for 10-days if patient is intubated and Azithromycin 500 mg IV on day 1, followed by 250 mg IV on days 2-5 (to prevent bacterial superinfection ).	Drug: Hydroxychloroquine, Azithromycin; FMTVDM Planar, SPECT, PET
Experimental: Treatment 2; Hydroxychloroquine 200 mg po q 8 hrs (600 mg qD) for a total of 10-days OR Hydroxychloroquine 155 mg IV every 8-hours (600 mg qD) for 10-days if patient is intubated and Doxycycline 100mg IV q 12 hrs with each dose given over 1 to 4-hours (to prevent bacterial superinfection ).	Drug: Hydroxychloroquine, Doxycycline; FMTVDM Planar, SPECT, PET
Experimental: Treatment 3; Hydroxychloroquine 200 mg po q 8 hrs (600 mg qD) for a total of 10-days OR Hydroxychloroquine 155 mg IV every 8-hours (600 mg qD) for 10-days if patient is intubated Clindamycin 150-450 mg po q6 hours x 10 days OR 4800 mg IV daily - beginning with 150 mg initial rapid infusion, followed by continuous infusion q 24-hours for 7-days.	Drug: Hydroxychloroquine, Clindamycin; FMTVDM Planar, SPECT, PET
Experimental: Treatment 4; Hydroxychloroquine 200 mg po q 8 hrs (600 mg qD) for a total of 10-days OR Hydroxychloroquine 155 mg IV every 8-hours (600 mg qD) for 10-days if patient is intubated Primaquine 200 mg po on day # 1. Clindamycin 150-450 mg po q6 hours x 10 days OR 4800 mg IV daily - beginning with 150 mg initial rapid infusion, followed by continuous infusion q 24-hours for 7-days.	Drug: Hydroxychloroquine, Clindamycin, Primaquine - low dose.; FMTVDM Planar, SPECT, PET
Experimental: Treatment 5; Primaquine 200 mg po on day # 1. Clindamycin 150-450 mg po q6 hours x 10 days OR 4800 mg IV daily - beginning with 150 mg initial rapid infusion, followed by continuous infusion q 24-hours for 7-days. This treatment arm is not available for intubated patients due to the absence of an IV form of Primaquine.	Drug: Hydroxychloroquine, Clindamycin, Primaquine - high dose.; FMTVDM Planar, SPECT, PET
Experimental: Treatment 6; Remdesivir 200 mg IV on day 1, followed by 100 mg IV qD for a total of 10-days.	Drug: Remdesivir; FMTVDM Planar, SPECT, PET
Experimental: Treatment 7; Tocilizumab 8mg/kg IV (not to exceed 800 mg) over 60-minutes. If clinical improvement is not noted, three additional doses may be administered at q 8-hour intervals from the initial infusion for a total of 4-doses maximum. ANY PATIENT DEMONSTRATING CYTOKINE RELEASE SYNDROME WILL HAVE THIS TREATMENT ARM AUTOMATICALLY ADDED.	Drug: Tocilizumab; FMTVDM Planar, SPECT, PET
Experimental: Treatment 8; Methylprednisolone 125 mg IV every 6-hours for 3 days; then 125 mg IV every 12-hours for 2 days; then 125 mg IV daily for 2 days; then 60 mg IV daily for 2 days [with each infusion given over 30-minutes]; then Solumedrol dose pack to taper off steroids.	Drug: Methylprednisolone; FMTVDM Planar, SPECT, PET
Experimental: Treatment 9; Interferon alpha-2b 5 million units per nebulizer BID.	Drug: Interferon-Alpha2B; FMTVDM Planar, SPECT, PET
Experimental: Treatment 10; Losartan 25 mg po qD. IRB held due to questions about benefit.	Drug: Losartan; FMTVDM Planar, SPECT, PET
Experimental: Treatment 11; Convalescent Plasma 2-units ABO-compatible with antibody titer of 1:320 dilution. Each unit intravenously infused over 4-hours.	Drug: Convalescent Serum; FMTVDM Planar, SPECT, PET

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in FMTVDM Measurement with nuclear imaging.	Measured improvement in tissue as measured using FMTVDM	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilator status	Extubation	7 days
Survival status	Self explanatory	30 days

Collaborators and Investigators

• Sponsor: The Camelot Foundation
• Investigators: Study Chair: Richard M Fleming, PhD, MD, JD, FHHI-OI-Camelot;QME

Publications and helpful links

Helpful Links

• FMTVDM Patent # 9566037
• The Critical Importance of Quantifying Tissue Change instead of using qualitative or semi-quanitified results.
• FMTVDM quantification.
• Infection and Inflammation reversal by treatment of pathogens with associated reductions in IL-6.

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2020
• Primary Completion (Actual): September 14, 2020
• Study Completion (Actual): September 14, 2020

Study Registration Dates

• First Submitted: April 11, 2020
• First Submitted That Met QC Criteria: April 14, 2020
• First Posted (Actual): April 16, 2020

Study Record Updates

• Last Update Posted (Actual): November 12, 2020
• Last Update Submitted That Met QC Criteria: November 10, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuroprotective Agents; Protective Agents; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Antimalarials; Methylprednisolone; Interferons; Interferon-alpha; Interferon alpha-2; Doxycycline; Losartan; Clindamycin; Clindamycin palmitate; Clindamycin phosphate; Primaquine; Azithromycin; Hydroxychloroquine; Remdesivir
• Other Study ID Numbers: FMTVDM2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data will be made available through electronic request from approved individuals and institutions.
• IPD Sharing Time Frame: This will depend upon the availability of staff given the multi-nation approach to this project.
• IPD Sharing Access Criteria: Expressed request through email as listed.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes