Small 72 patient RCT of ivermectin and ivermectin + doxycycline showing faster recovery with ivermectin. The ivermectin + doxycycline group uses only a single dose of ivermectin vs. 5 daily doses for the ivermectin group. PCR testing was only done weekly after day 7, therefore hospitalization time may not match symptomatic recovery.
Ivermectin group: 12mg daily for 5 days
Ivermectin + doxycycline: 12mg ivermectin single dose, 200mg doxycycline + 100mg bid 4 days
This is the
8th of 46 COVID-19 RCTs for ivermectin, which collectively show efficacy with
p=0.00000014.
This is the
24th of 99 COVID-19 controlled studies for ivermectin, which collectively show efficacy with
p<0.0000000001 (1 in 2 sextillion).
|
risk of unresolved symptoms, 85.0% lower, RR 0.15, p = 0.09, treatment 0 of 17 (0.0%), control 3 of 19 (15.8%), NNT 6.3, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 7, fever, ivermectin (5 days), primary outcome.
|
|
risk of unresolved symptoms, 62.7% lower, RR 0.37, p = 0.35, treatment 1 of 17 (5.9%), control 3 of 19 (15.8%), NNT 10, day 7, fever, ivermectin (1 day) + doxycycline.
|
|
risk of no viral clearance, 75.6% lower, HR 0.24, p = 0.03, treatment 11 of 22 (50.0%), control 20 of 23 (87.0%), NNT 2.7, adjusted per study, inverted to make HR<1 favor treatment, day 7, ivermectin (5 days).
|
|
risk of no viral clearance, 56.5% lower, HR 0.43, p = 0.22, treatment 16 of 23 (69.6%), control 20 of 23 (87.0%), NNT 5.8, adjusted per study, inverted to make HR<1 favor treatment, day 7, ivermectin (1 day) + doxycycline.
|
|
risk of no viral clearance, 63.0% lower, HR 0.37, p = 0.02, treatment 5 of 22 (22.7%), control 14 of 23 (60.9%), NNT 2.6, adjusted per study, inverted to make HR<1 favor treatment, day 14, ivermectin (5 days).
|
|
risk of no viral clearance, 41.2% lower, HR 0.59, p = 0.19, treatment 9 of 23 (39.1%), control 14 of 23 (60.9%), NNT 4.6, adjusted per study, inverted to make HR<1 favor treatment, day 14, ivermectin (1 day) + doxycycline.
|
|
time to viral-, 23.6% lower, relative time 0.76, p = 0.02, treatment 22, control 23, ivermectin (5 days).
|
|
time to viral-, 9.4% lower, relative time 0.91, p = 0.27, treatment 23, control 23, ivermectin (1 day) + doxycycline.
|
|
hospitalization time, 1.0% lower, relative time 0.99, treatment 22, control 23, ivermectin, PCR testing only done weekly after day 7.
|
|
hospitalization time, 4.1% higher, relative time 1.04, treatment 23, control 23, ivermectin + doxycycline, PCR testing only done weekly after day 7.
|
|
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
|
Ahmed et al., 2 Dec 2020, Double Blind Randomized Controlled Trial, Bangladesh, peer-reviewed, mean age 42.0, 15 authors, average treatment delay 3.83 days, dosage 12mg days 1-5, the ivermectin + doxycycline group took only a single dose of ivermectin.
A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness
Sabeena Ahmed, Mohammad Mahbubul Karim, Allen G Ross, Mohammad Sharif Hossain, John D Clemens, Mariya Kibtiya Sumiya, Ching Swe Phru, Mustafizur Rahman, Khalequ Zaman, Jyoti Somani, Rubina Yasmin, Mohammad Abul Hasnat, Ahmedul Kabir, Asma Binte Aziz, Wasif Ali Khan
International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.11.191
Ivermectin, a US Food and Drug Administration-approved anti-parasitic agent, was found to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in vitro. A randomized, double-blind, placebo-controlled trial was conducted to determine the rapidity of viral clearance and safety of ivermectin among adult SARS-CoV-2 patients. The trial included 72 hospitalized patients in Dhaka, Bangladesh, who were assigned to one of three groups: oral ivermectin alone (12 mg once daily for 5 days), oral ivermectin in combination with doxycycline (12 mg ivermectin single dose and 200 mg doxycycline on day 1, followed by 100 mg every 12 h for the next 4 days), and a placebo control group. Clinical symptoms of fever, cough, and sore throat were comparable among the three groups. Virological clearance was earlier in the 5-day ivermectin treatment arm when compared to the placebo group (9.7 days vs 12.7 days; p = 0.02), but this was not the case for the ivermectin + doxycycline arm (11.5 days; p = 0.27). There were no severe adverse drug events recorded in the study. A 5-day course of ivermectin was found to be safe and effective in treating adult patients with mild COVID-19. Larger trials will be needed to confirm these preliminary findings.
Ethical review The trial was approved by the Institutional Review Board (Research Review Committee and Ethical Review Committee) of icddr,b and subsequently by the National Ethics Review Committee of Bangladesh Medical Research Council and Clinical Trial Advisory Committee of the Directorate General of Drug Administration, Government of Bangladesh. Written informed consent was obtained from all patients.
Declaration of interests The authors declare that there are no known competing financial interests or personal relationships that could have appeared to influence the work described in this paper.
Conflicts of interest The authors have no conflicts of interest to declare.
Author agreement All authors have seen and approved the final version of the manuscript being submitted. The article is the authors' original work, has not received prior publication, and is not under consideration for publication elsewhere.
References
Alam, Murshed, Bhiuyan, Saber, Alam, A Case Series of 100 COVID-19 Positive Patients Treated with Combination of Ivermectin and Doxycycline, J Bangladesh Coll Physic Surg,
doi:10.3329/jbcps.v38i0.47512Caly, Druce, Catton, Jans, Wagstaff, The FDA-approved Drug Ivermectin inhibits the replication of SARS-CoV-2 in vitro Antiviral Res
Chiu, Lu, Metabolism and tissue residues
Lespine, Alvinerie, Sutra, Pors, Chartier, Influence of the route of administration on efficacy and tissue distribution of ivermectin in goat, Vet Parasitol
Rajter, Sherman, Fatteh, Vogel, Sacks et al., ICON (Ivermectin in COvid Nineteen) study: use of ivermectin is associated with lower mortality in hospitalised patients with COVID-19, medRxiv
Wu, Liu, Yang, Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods, Acta Pharm Sin B,
doi:10.1016/j.apsb.2020.02.008
