The Fleming [FMTVDM] Directed CoVid-19 Treatment Protocol

Sponsor

The Camelot Foundation (Other)

Overall Status

Completed

CT.gov ID

NCT04349410

Collaborator

(none)

1,800

Enrollment

Location

Arms

5.1

Actual Duration (Months)

351.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
CoVid 19 Positive	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	Phase 2/Phase 3

Detailed Description

FMTVDM - See Appendix A.

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.
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.
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.

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.
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.
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 Design

Study Type:

Interventional

Actual Enrollment :

1800 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Intervention Model Description:

Measurement of CoVid-19 pneumonia (CVP) and inflammation will be made using a patented method (FMTVDM #9566037 and adjunct USPTO submissions deemed covered by USPTO under the original patent #9566037). Following FMTVDM measurements, patients will be randomized into one of eleven treatment arms - others may be added as information becomes available. Forty-eight to 72-hours later - providing adequate time for treatment effect - FMTVDM will be repeated. Patients with improvement in FMTVDM will be maintained on their original treatment. FMTVDM measured treatment failure will result in a change to another arm of treatment. FMTVDM measurement showing no change will be treated by adding an additional treatment arm to patient care. Sequential FMTVDM studies will be carried out. Simultaneous Immune and ventilatory RX. Ventilatory support per ARDS protocol. Applicable blood tests and PCR will be included.Measurement of CoVid-19 pneumonia (CVP) and inflammation will be made using a patented method (FMTVDM #9566037 and adjunct USPTO submissions deemed covered by USPTO under the original patent #9566037). Following FMTVDM measurements, patients will be randomized into one of eleven treatment arms - others may be added as information becomes available. Forty-eight to 72-hours later - providing adequate time for treatment effect - FMTVDM will be repeated. Patients with improvement in FMTVDM will be maintained on their original treatment. FMTVDM measured treatment failure will result in a change to another arm of treatment. FMTVDM measurement showing no change will be treated by adding an additional treatment arm to patient care. Sequential FMTVDM studies will be carried out. Simultaneous Immune and ventilatory RX. Ventilatory support per ARDS protocol. Applicable blood tests and PCR will be included.

Masking:

Single (Investigator)

Masking Description:

As FMTVDM is an absolute quantification method, which cannot be influenced by human error or bias, the final determinant of success or failure of treatment cannot be influenced. However, given the pandemic, medical, nursing, technologist and other healthcare providers will NOT be blinded to data. The availability of the data will allow real time assessment and decision making by the clinicians involved in the care of the patient.

Primary Purpose:

Treatment

Official Title:

The Fleming [FMTVDM] Directed CoVid-19 Treatment Protocol

Actual Study Start Date :

Apr 11, 2020

Actual Primary Completion Date :

Sep 14, 2020

Actual Study Completion Date :

Sep 14, 2020

Arms and Interventions

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