An Outpatient Clinical Trial Using Ivermectin and Doxycycline in COVID-19 Positive Patients at High Risk to Prevent COVID-19 Related Hospitalization

NCT ID: NCT04729140

Last Updated: 2021-04-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-28
• Study Completion Date: 2022-03-28

Brief Summary

The purpose of this Clinical trial is to explore the therapeutic benefits of Ivermectin and Doxycycline in different combinations in high risk patients diagnosed with COVID-19.

Detailed Description

Purpose of the study:

The purpose of this Clinical trial is to explore the therapeutic benefits of Ivermectin and Doxycycline in different combinations. The investigators are studying known medications at already FDA approved dosages for therapeutic benefit. The investigators are not seeking new indications for these medications.

Null Hypothesis:

The investigators hypothesize that treating high-risk populations positive for COVID-19 illness with Ivermectin, Doxycycline, or Ivermectin only in the outpatient setting will decrease hospitalizations related to COVID-19 illness in comparison with Placebo.

Sample Size: Minimum of 50 high risk COVID 19 positive patients who volunteer and provide consent to participate in this study to be placed in three different groups (A,B,C). Subjects are to be randomized 1:1:1 and enrolled in sequential order to Group A, then B, then C as they enroll. This distribution pattern will be followed for the entirety of the study.

Group A: Ivermectin plus Doxycycline Group B: Ivermectin plus Placebo Group C: Placebo plus Placebo

Drug Dosing schedule:

Group A: Ivermectin 200 mcg/kg on day 1 and day 2-plus doxycycline 100 mg tablets twice a day for seven days

Group B: Ivermectin 200 mcg/kg on day 1 and day 2-plus placebo tablet twice a day for seven days

Group C: Placebo (number of tablets according to weight) plus placebo twice a day for seven days

Body Weight (kg) Table for tablets of Ivermectin

15-24 kg 1 tablet 25-35 kg 2 tablets 36-50 kg 3 tablets 51-65 kg 4 tablets 66-79 kg 5 tablets 80-109 kg 6 tablets >110 kg 7 tablets

The designated pharmacy will provide pre-packed treatment to patients based on the order of enrollment to the clinical trial.

Methods:

(A) Upon diagnosis of COVID-19 with NAAT-PCR or Rapid Antigen Test for SARS-COV 2, patients will be evaluated by their primary care physician who will consider the health risk of patients and provide all alternatives. Primary care physicians will recommend these patients to a treatment hotline number. Patients can also self refer to the treatment hot line. Patients will call this provided hotline number, and if they wish to be a part of the above said clinical trial, it will connect them to the Principal Investigator's (Dr Werther Marciales) Team. Based on inclusion and exclusion criteria, patients will be assigned to one of three different study groups outlined above. Each participant in all randomized groups will receive treatment as specified above as soon as the patient signs consent and agrees to participate in said clinical trial. Patient's subjective data including but not limited to age, gender, height, weight, detailed medical history, or any objective data will be collected and kept confidential.

(B) Patients will undergo blood work (CBC, CMP, Ferritin, D-dimer, CRP, CK, PT/INR, PTT and Fibrinogen, Interleukin 6 level,TNF alpha level, IL6 receptor level and TNF alpha receptor level) at baseline. Blood work will be repeated on days 7 and 14. These medications used in the clinical study will have a good safety profile, which has been tested over a period of time. All patients enrolled in the trial will be thoroughly evaluated prior to detailed history, especially regarding home medications, and severe co-morbid conditions as listed in the exclusion criteria.

(C) During the clinical trial, the study doctor, or the subject's primary care provider will be involved in treatment of subjects if and when there are any adverse reactions or if subjects need additional care. If a patient's COVD-19 relayed symptoms worsen then, he/she would be admitted to the hospital for further care, including mechanical ventilation if required. These patients clinical data will be followed for the remainder of he hospitalization. A patient admitted to the hospital for COVID-19 related illness will be considered to reach outcome.

Criteria for admission of confirmed COVID-19:

A patient must have COVID-19 illness and at least one of the following two conditions:

1. At least 2 of the CURB-65 criteria

2. SpO2 <93% on room air or a 4% decrease from baseline

CURB 65 criteria

1. Confusion of new onset

2. Blood Urea Nitrogen greater then 7 mmol/L (19 mg/dl)

3. Respiratory rate of 30 breaths per minute or greater

4. Blood Pressure less then 90 mm Hg systolic or 60 mm Hg diastolic

5. Age 65 or older

(D) Patients will be advised to quarantine themselves and record their temperature twice daily and maintain a home log. Patients will obtain a pulse oximeter to monitor their oxygen levels at least twice a day. Patients will also be submitted to symptoms questionnaire or ARDS questionnaire either in person or over telephone or through televist twice a week for total of five weeks.

(E) All treatment groups will also be monitored for any adverse events related to medication therapy during treatment and for 4 weeks thereafter on a twice a week basis using ADR Monitoring form. All moderate and severe adverse drug reactions will be notified to the principal investigator for immediate actions, which might include discontinuation of therapy after establishing a causal relationship. All adverse drug reactions will be recorded and reported to the FDA using Form 3500, which will be faxed to 1 800 FDA 0178. Due to the severe nature of transmissibility of COVID-19 and the importance of minimizing human interaction and preservation of Personal Protective Equipment, patients will be followed either in person, telephonically or via Televisit. Exclusion Criteria will mitigate the risk of involving patients susceptible to side effects of study treatment medications.

Data Analysis:

The total sample size is estimated at 150 participants (Minimum 50 patients in each group). The one-way analysis of variance (ANOVA) will compare group differences at baseline, midpoint, and endpoint. Data analysis will be carried out using statistical package for the social sciences software (SPSS). Interim data analysis will be performed at three different levels of the number of participants starting at sample size 20, 30 and 50. If no significant findings are obtained from the data at N=50, then it will add more participants to the study to achieve statistical significance. Sponsor and Principal Investigator will defer data analysis to a statistician. A Data Monitoring Committee (DMC) is going to be established in order to review accumulating trial data by treatment group in order to monitor patient safety and efficacy, ensure validity and integrity of the trial and make benefit-risk assessment. This is going to be conducted by a third party external DMC.

Ethical Considerations:

Informed consent will be obtained via phone, telecommunications, or in person and a copy of the consent will be sent to the subjects via postal mail, email or both. All information will be kept confidential. For research records, name, social security number, address, or phone number will not identify patients. In the event of any publication or presentation resulting from the research, no personally identifiable information will be shared. The investigators will keep the patients participation in the research study confidential to the extent permitted by law. Patient identifiers might be removed from data and, after such removal, the data could be used for future research or distributed to another investigator for future studies without additional informed consent from the subject.

Resources:

There is no funding available at this time, and the study will be self sponsored by MAX HEALTH.

Compensation:

There is no compensation offered as part of participation in this study.

Cost:

Patients will be charged for any services that are performed as part of their clinical care. Patients will not be compensated for travel or time. Patients are required to get their medication (s) used in the clinical trial from a dedicated pharmacy. Study drugs will be provided to the patients at no cost to the patient.

Removal from this study:

The patient may elect to withdraw from the study at any point. During the clinical trial, if a patients COVID-19 related symptoms worsen, then they would admitted to the hospital for further care, including mechanical ventilation if required, and the clinical data from this subset of patients will not be used for statistical consideration of this study. Still, these patients clinical data will be followed for the remainder of the hospitalization.

Conditions

Covid19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Ivermectin plus Doxycycline

Ivermectin 200 mcg/kg on day 1 and day 2-plus doxycycline 100 mg tablets twice a day for seven days

Body Weight (kg) Single oral Dose number of 3 mg tablets of Ivermectin

15-24 kg 1 tablet

25-35 kg 2 tablets

36-50 kg 3 tablets

51-65 kg 4 tablets

66-79 kg 5 tablets

80-109 kg 6 tablets

>110 kg 7 tablets

Group Type: ACTIVE_COMPARATOR

Ivermectin Tablets

Intervention Type: DRUG

Double-blinded, prospective, placebo controlled outpatient randomized clinical trial.

Doxycycline Tablets

Intervention Type: DRUG

Double-blinded, prospective, placebo controlled outpatient randomized clinical trial.

Ivermectin plus Placebo

Ivermectin 200 mcg/kg on day 1 and day 2-plus placebo tablet twice a day for seven days

Body Weight (kg) Single oral Dose number of 3 mg tablets of Ivermectin and Placebo

15-24 kg 1 tablet

25-35 kg 2 tablets

36-50 kg 3 tablets

51-65 kg 4 tablets

66-79 kg 5 tablets

80-109 kg 6 tablets

>110 kg 7 tablets

Group Type: ACTIVE_COMPARATOR

Ivermectin Tablets

Intervention Type: DRUG

Double-blinded, prospective, placebo controlled outpatient randomized clinical trial.

Placebo

Intervention Type: DRUG

Double-blinded, prospective, placebo controlled outpatient randomized clinical trial.

Placebo plus Placebo

Placebo (number of tablets according to weight) plus placebo twice a day for seven days

Body Weight (kg) Single oral Dose number of 3 mg tablets of Placebo

15-24 kg 1 tablet

25-35 kg 2 tablets

36-50 kg 3 tablets

51-65 kg 4 tablets

66-79 kg 5 tablets

80-109 kg 6 tablets

>110 kg 7 tablets

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Double-blinded, prospective, placebo controlled outpatient randomized clinical trial.

Interventions

Ivermectin Tablets

Double-blinded, prospective, placebo controlled outpatient randomized clinical trial.

Intervention Type: DRUG

Doxycycline Tablets

Double-blinded, prospective, placebo controlled outpatient randomized clinical trial.

Intervention Type: DRUG

Placebo

Double-blinded, prospective, placebo controlled outpatient randomized clinical trial.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age greater than or equal to 18
• Willing and able to provide verbal /telephonic/Personal or computer based Informed Consent
• Experiencing symptoms of COVID-19 illness and tested positive for SARS CoV-2 with either PCR, NAAT or antigen testing
• Residents in a Nursing Home or long-term care facility
• Immunocompromised state, including solid organ transplant, HIV infection, other immune deficiency, immunosuppressant medication including systemic corticosteroids
• Chronic lung disease, including Chronic Obstructive Pulmonary Disease (COPD), moderate to severe asthma, cystic fibrosis, pulmonary fibrosis
• Cardiovascular Disease
• Cancer
• Hypertension
• Obesity (body mass index [BMI greater then or equal to 30 kg/m^2]
• Diabetes Mellitus
• Chronic Kidney Disease
• Chronic Liver Disease
• Cerebrovascular Disease
• Neurological Disorders including dementia
• Tobacco use disorders
• Hematologic disorders, including sickle cell disease and thalassemia

• Health care professionals and firefighters.
• Government officials or employees.
• Students and teachers.
• Law enforcement agents and personnel.
• Individuals who live with, and cannot isolate, from any of the above groups.

Exclusion Criteria

• Participants under the age of 18
• Received any COVID vaccine within the last 30 days
• Contraindications to Ivermectin or Doxycycline
• History of Seizure Disorder or Epilepsy
• History of Myocardial Infarction or Heart Attack within the last one month
• Already receiving Ivermectin or Doxycycline for treatment of any other disease or disorder
• Allergies to Ivermectin or Doxycycline including angioedema, severe asthma, exfoliative dermatitis, Steven Jonson syndrome or psoriasis
• History of angioedema, exfoliative dermatitis, Steven Johnson syndrome, psoriasis
• Currently Pregnant or planning to conceive soon
• Breastfeeding
• History of prior Clostridium Difficile infection

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Max Health, Subsero Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Werther Marciales, MD

Role: PRINCIPAL_INVESTIGATOR

Clinical Trial Principal Investigator

Ryan Salom

Role: PRINCIPAL_INVESTIGATOR

sub Clinical Trial Prinicipal Investigator

Faheem Ahmad, MD

Role: PRINCIPAL_INVESTIGATOR

sub Clinical Trial Prinicipal Investigator

Divisha Sharma, MD

Role: PRINCIPAL_INVESTIGATOR

Clinical Trial Investigator

Nicholas Guy Ross, DO

Role: PRINCIPAL_INVESTIGATOR

Clinical Trial Investigator

Terry Fredeking

Role: PRINCIPAL_INVESTIGATOR

Clinical Trial Investogator

Michael Ricciardi, PhD

Role: PRINCIPAL_INVESTIGATOR

Clinical Trial Investogator

Locations

MAX HEALTH, Subsero Health 2055 Wood Street, Suite 100

Sarasota, Florida, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Inita Bedi

Role: CONTACT

ibedi@mymaxdoc.com

941 371 3500

Werther Marciales, MD

Role: CONTACT

werther40@msn.com

941 545 8857

Facility Contacts

Inita Bedi

Role: primary

ibedi@mymaxdoc.com

941-371-3500

Werther Marciales, MD

Role: backup

werther40@msn.com

941 545 8857

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Other Identifiers

COVIVER-OUT PLUS

Identifier Type: -

Identifier Source: org_study_id