Clinical Trial of Ivermectin Plus Doxycycline for the Treatment of Confirmed Covid-19 Infection

OBJECTIVES:

General objectives:

To observe the benefit (clinical and microbiological) of Ivermectin and Doxycycline in
Confirmed Covid 19 cases.

Specific objectives:

1. To observe the clinical outcome in trial group and the placebo group.

2. To observe the duration require controlling viral replication (negative RT-PCR) in the
trial and placebo group.

3. To compare the outcome between the two groups.

RATIONALE:

Covid-19 is an emergent pandemic, threatens the life of millions of the people throughout the
globe. There is increasing effort of the scientist to unveil a remedy of covid-19. Still it
is unsuccessful. At present there is no other alternative other than experimenting the
existent drug against the virus. There are several trials going throughout the globe. Among
them Ivermectin showed good efficacy in vitro trial. Some clinical trial also proved it
beneficial. The Doxycycline also has some anti viral role with its prominent
anti-inflammatory role. Synergistic action of the two drugs might be proved some benefit in
clinical trial. As both drugs are cheap and less toxic, if it does, it would be the blessing
for the poor people of the globe.

METHODOLOGY:

Study type: Interventional Clinical trial Estimated enrollment: 200 participants per group

For superior trial, the formula is:

N=size per group; p=the response rate of standard treatment group; p0= the response rate of
new drug treatment group; zx= the standard normal deviate for a one or two sided x; d= the
real difference between two treatment effect; δ0= a clinically acceptable margin; S2= Polled
standard deviation of both comparison groups.

All parameters were assumed as follows: p =0.40; p0=0.58; α=0.05;β=0.20; δ=0.18; δ0=0.10.

However, we are assuming that lost to follow up or refuse to include in trial will be 20%,
that means 24. So at least 150 patients will be allocated randomly and power of this study
will be 80%.

Allocation: Randomized Intervention model: Parallel assignment Intervention model
description: Patient will be randomized 1:1 to placaebo with standard care and combined
doxycycline and ivermectin with standard care.

Blinding: Double blind (The participant and the clinicians/data collectors will be unaware of
the treatment the participant receives) Primary purpose: Treatment Official title: A phase
III trial to promote recovery from covid 19 with combined Doxycycline and Ivermectin along
standard care. Provider of placebo and active ingredients: Popular pharmaceutical limited
Dosage of the drugs: Ivermactin 6 mg 2 tab stat, cap Doxycycline 100 mg 1 cap BD 5 days

Data collection technique:

Data will be collected by assigned. trained data collectors (Physician). Patient will be
enrolled according to defined inclusion and exclusion criteria in the current research.
Informed written consent will be obtained from the patient or their relatives. Each patient
participating in the trial will be uniquely identified, and information such as his name,
address is recorded in the trial 'subject number list'. Only the principle investigator will
be aware about the allocation of the drugs. The patients and the data collectors will be
unaware about the group allocation of the drugs. The Data will be reviewed by the
co-investigators. It will be managed by principle and co-principle investigators in
designated computer.

Clinical assessment (fever, cough, Anorexia, Temperature, pulse, blood pressure, respiratory
rate, oxygen saturation) will be done every day. Routine investigation (CBC, ESR, CRP,
Creatinine, RBS, SGPT, chest x-ray, D- Dimer) will be done at admission and at day 3, 5, 7,
10 and 14 day. In case of the clinical deterioration it would done according to necessity.
RT-PCR will be done at day-0, Day 5, day 7 and day 14.

Standard care: both the experimental and placebo will receive the available standard of care,
like-

- Paracetamol, Antihistamine, Cough suppressant, Vitamins

- Oxygen therapy according to indication and need

- Low molecular weight heparin according to indication

- Appropriate other broad spectrum antibiotics

- Other drugs for associated co- morbid condition

Management of the adverse events:

Drugs adverse effect will be monitored by a defined committee. The patient experiencing
adverse effect of the drugs will be discontinued from the study. It will be managed with
priority to the highest possible level by the hospital authority as well as the
investigators.

If the patient progresses from mild to moderate or severe disease, the study will be
continued and available management of the appropriate severity will be immediately started.
The patient will be monitored closely.

Data analysis:

Data will be analyzed by computer with the help of SPSS (Statistical Package for Social
Sciences) version 26. Unpaired t-test would be used for testing quantitative data and for
testing qualitative data two sample z- test will be used. Comparing drug outcome in between
two groups hazard ratio, Kaplan-Meire curve will be used.

Dropout management: Likelihood based methods such as mixed models will be used to estimate
unbiased treatment effects, under assumptions regarding the missingness mechanisms.