Hospitals Using MATH+ Protocol 2022

For comprehensive information on the MATH+ protocol, please refer to their peer-reviewed publication: MATH+ protocol for the treatment of SARS-CoV-2 infection: the scientific rationale and the included references.

The authors and their affiliated hospitals include:

Paul E Marik
Eastern Virginia Medical School Norfolk, Virginia

Pierre Kory
President, Frontline COVID-19 Critical Care Alliance (FLCCC Alliance)

Joseph Varon
Department of Critical Care Medicine, United Memorial, Medical Center, Houston, TX, USA.

Jose Iglesias
  • Department of Nephrology and Critical Care, Hackensack Meridian School of Medicine at Seton Hall University, Nutley, NJ, USA.
  • Department of Nephrology and Critical Care, Community Medical Center, Toms River, NJ, USA.
G Umberto Meduri
  • Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
  • Memphis Veterans Affairs Medical Center, Memphis, TN, USA.
You can find a listing of physicians and hospitals who use the FLCCC MATH+, I-MASK+, I-MASS or I-RECOVER protocols in whole or in part, or plan to do so in the near future on the FLCCC Alliance Directory. Do take note that the directory is mixed with hospitals from other countries. You will need to key in your location in United States in the 'search' box in order to find a short-listed list of doctors and hospitals at or near your location. Most of the listing on this directory are doctors affiliated with clinics. You might also find a few doctors affiliated with hospitals. Do contact them directly to confirm.

If you wish to look for a listing of doctors who can prescribe ivermectin and other necessary medicines for early treatment, check out our Find a Provider post. You can also find updated protocols for:

To assist all who are having difficulty finding pharmacists to fill prescriptions for ivermectin for preventing or treating COVID-19, check out Find a Pharmacy to fill Ivermectin (US).

Related: Dr. Paul Marik: "Patients at Sentara Norfolk General Hospital are Dying Needlessly."

MATH+ Protocol

MATH+ protocol

The MATH+ Hospital Treatment Protocol for COVID-19 is designed for hospitalized patients, to be initiated as soon as possible after they develop respiratory difficulty and require oxygen supplementation. We've posted the MATH+ protocol below.

The three core pathophysiologic processes that have been identified are severe hypoxemia, hyperinflammation, and hypercoagulability. This combination medication protocol is designed to counteract these processes either through the use of single agents or in synergistic actions. A unique insight into this disease made by members of our group is that the majority of patients initially present with an inflammatory reaction in the lungs called “organizing pneumonia,” which is the body’s reaction to injury and is profoundly responsive to corticosteroid therapy. If the organizing pneumonia response is left untreated or presents as a rapidly progressive sub-type, a condition called Acute Respiratory Distress Syndrome (ARDS) follows.

The two main therapies that can reverse and/or mitigate the extreme inflammation causing ARDS are the combination of the corticosteroid Methylprednisolone and the antioxidant Ascorbic acid, which is given intravenously and in high doses. Both of these medicines have multiple synergistic physiologic effects and have been shown in multiple randomized controlled trials to improve survival in ARDS, particularly when given early in the disease. Thiamine is given to optimize cellular oxygen utilization and energy consumption, protecting the heart, brain, and immune system. Given the numerous clinical and scientific investigations that have demonstrated consistent, reproducible, and excessive levels of hyper-coagulation, particularly in the severely ill, the anticoagulant Heparin is used to both prevent and help in dissolving blood clots that appear with a very high frequency. The “+” sign indicates several important co-interventions that have a combination of strong physiologic rationale with existing or emerging pre-clinical and clinical data to support their use in similar conditions or in COVID-19 itself, and all with a well-established safety profile. Such adjunctive therapies are continuously being evaluated and amended as the published medical evidence evolves.

Timing is a critical factor in the efficacy of MATH+ and to achieving successful outcomes in patients ill with COVID-19. Patients must go to the hospital as soon as they experience difficulty breathing or have a low oxygen level. The MATH+ protocol should be administered soon after a patient meets criteria for oxygen supplementation (within the first hours after arrival in the hospital), in order to achieve maximal efficacy. Delayed therapy can lead to complications such as the need for mechanical ventilation. If administered early, the MATH+ formula of FDA-approved, safe, inexpensive, and readily available drugs may eliminate the need for ICU beds and mechanical ventilators and return patients to health.

Current MATH+ protocol: version 15, updated on Sept. 18, 2021

A. CORE MEDICATION

Methylprednisolone

A. Upon oxygen requirement or abnormal chest X-ray
  • Preferred: 80mg IV bolus, then 40mg IV twice daily 
  • Alternate: 80mg / 240ml normal saline IV infusion at 10ml/hr 
  • Follow COVID-19 Respiratory Failure protocol: www.flccc.net/respiratory-support-c19
A1. If no improvement in oxygenation in 1–3 days, double dose to 160mg/daily. 
A2. Upon need for FIO2 > 0.6 or ICU, escalate to “Pulse Dose” below (B) 
A3. Once off IMV, NPPV, or High flow O2, decrease to 20mg twice daily. Once off O2, then taper with 20mg/day × 5 days then 10mg/day × 5 days

B. Refractory Illness/ Cytokine Storm
  • “Pulse” dose with 1 gram daily × 3 days
  • Continue × 3 days then decrease to 160mg IV/ daily dose above, taper according to oxygen requirement (A). If no response or CRP/Ferritin high/rising, consider mega-dose IV ascorbic acid and/or “Therapeutic Plasma Exchange” below
Ascorbic Acid

O2 < 4L on hospital ward 
  • 500–1000mg oral every 6 hours 
  • Until discharge
O2 > 4 L or in ICU 
  • 50mg/kg IV every 6 hours 
  • Up to 7 days or until discharge from ICU, then switch to oral dose above
If in ICU and not improving 
  • Consider mega-doses: 25 grams IV twice daily for 3 days 
  • Completion of 3 days of therapy
Thiamine

ICU patients 
  • 200mg IV twice daily 
  • Up to 7 days or until discharge from ICU
Heparin (Low Molecular Weight Heparin)

If initiated on a hospital ward 
  • 1mg/kg twice daily — monitor anti-Xa levels, target 0.6–1.1 IU/ml 
  • Until discharge then start DOAC at half dose × 4 weeks
If initiated in the ICU 
  • 0.5mg/kg twice daily — monitor anti-Xa levels, target 0.2–0.5 IU/ml
  • Until discharge then start DOAC at half dose × 4 weeks

B. First Line Adjunctive Therapy (use in all hospitalized patients)

Ivermectin  
  • Hospitalized patients 
  • 0.6 mg/kg per dose — daily 2 (take with or after a meal) 
  • For 5 days or until recovered
Nitazoxanide 
  • Hospitalized patients 
  • 500mg twice daily — (take with or after a meal) 
  • For 5 days or until recovered
Dual Anti-Androgen Therapy 
  • Hospitalized patients 
    • 1. Spironolactone 100mg twice daily 
    • 2. Dutasteride 2mg on day 1, followed by 1mg daily — or Finasteride 10mg daily 
  • 14 days or until discharge from hospital
  • ICU Patients 
    • 1. Flutamide 250mg TID — or Bicalutamide 150mg daily 
    • 2. Dutasteride 2mg on day 1, followed by 1mg daily — or Finasteride 10mg daily 
  • 14 days or until discharge from hospital
Vitamin D 
  • Hospitalized patients 
  • Calcitriol: 0.5mcg on day 1, then 0.25mcg daily 
  • 7 days
Melatonin 
  • Hospitalized patients 
  • 6–12mg PO at night 
  • Until discharge

C. Second Line Adjunctive Therapy (use in addition to first line adjunctive therapies in all ICU patients)

Fluvoxamine 
  • Hospitalized patients 
  • 50mg PO twice daily — consider fluoxetine 30mg daily as an alternative (it is often better tolerated) 
  • 10–14 days
Cyproheptadine 
  • If any of: 1) on fluvoxamine, 2) hypoxemic, 3) tachypneic/respiratory distress, 4) oliguric/ kidney injury 
  • 8mg — 3 x daily 
  • until discharge, slow taper once sustained improvements noted
Zinc 
  • Hospitalized patients 
  • 75–100mg PO daily 
  • Until discharge
Famotidine 
  • Hospitalized Patients 
  • 40–80mg PO twice daily 
  • Until discharge
Atorvastatin 
  • ICU Patients 
  • 80mg PO daily 
  • Until discharge
Therapeutic Plasma Exchange 
  • Patients refractory to pulse dose steroids 
  • 5 sessions, every other day 
  • Completion of 5 exchanges


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