Summary of COVID-19 doxycycline studies

1. Mahmud et al., Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial

366 patient doxycycline early treatment RCT: 86% lower mortality (p=0.25), 57% lower progression (p=0.001), 94% improved recovery (p<0.0001), and 39% improved viral clearance (p=0.002).
RCT for ivermectin+doxycycline showing improvements in mortality, recovery, progression, and virological cure. 183 treatment and 183 control patients with no deaths in the treatment arm vs. 3 in the control arm (the 3 control deaths are not included in the analysis of other outcomes). Results may reflect the use of ivermectin, doxycycline, and potential synergistic effects of the combination. In the PRINCIPLE trial, no mortality benefit was seen for doxycycline alone [thelancet.com] (0.6% mortality with doxycycline vs. 0.2% control).
Oct 2020, J. Int. Medical Research, https://journals.sagepub.com/doi/10.1177/03000605211013550, https://c19p.org/mahmuddox

2. Stambouli et al., COVID-19 prophylaxis with Doxycycline and Zinc in Health Care Workers: A prospective randomized double-blind clinical tria

113 patient doxycycline prophylaxis RCT: 64% fewer cases (p=0.04) and 15% improved viral load (p<0.0001).
Prophylaxis RCT with 59 zinc + doxycycline, 56 doxycycline, and 57 placebo healthcare workers, showing lower symptomatic cases and significantly improved Ct values with the addition of zinc to doxycycline treatment. Doxycycline 100mg/day and zinc 15 mg/day.
Jun 2022, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971222003496, https://c19p.org/stamboulidox

3. Hashim et al., Controlled randomized clinical trial on using Ivermectin with doxycycline for treating COVID-19 patients in Baghdad, Iraq

140 patient doxycycline late treatment RCT: 92% lower mortality (p=0.03), 83% lower progression (p=0.07), and 41% faster recovery (p=0.0001).
RCT 70 ivermectin+doxycycline patients and 70 control patients showing reduced time to recovery and reduced mortality with treatment. Earlier treatment was more successful. For ethical reasons, critical patients were all in the treatment group. NCT04591600.
Oct 2020, Iraqi J. Medical Science, http://www.iraqijms.net/upload/pdf/iraqijms60db8b76d3b1e.pdf, https://c19p.org/hashimdox

4. Butler et al., Doxycycline for community treatment of suspected COVID-19 in people at high risk of adverse outcomes in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial

1,728 patient doxycycline late treatment RCT: 12% higher combined mortality/hospitalization (p=0.59), 51% lower ventilation (p=0.48), 45% lower ICU admission (p=0.36), and 2% lower need for oxygen therapy (p=0.95).
RCT 2,508 high-risk patients (aged ≥65 or ≥50 with comorbidities) showing no significant benefit with doxycycline.
Sep 2021, The Lancet Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S2213260021003106, https://c19p.org/butler

5. Spoorthi et al., Utility of Ivermectin and Doxycycline combination for the treatment of SARSCoV-2

100 patient doxycycline late treatment study: 21% faster recovery (p=0.03) and 16% shorter hospitalization (p=0.01).
100 patient prospective trial of ivermectin + doxycycline showing reduced time to symptom resolution and shorter hospital stay with treatment.
Nov 2020, IAIM, 2020, 177-182, http://iaimjournal.com/wp-content/uploads/2020/10/iaim_2020_0710_23.pdf, https://c19p.org/spoorthidox

6. Ahsan et al., Clinical Variants, Characteristics, and Outcomes Among COVID-19 Patients: A Case Series Analysis at a Tertiary Care Hospital in Karachi, Pakistan

165 patient doxycycline late treatment study: 50% lower mortality (p=0.03).
Retrospective 165 hospitalized patients in Pakistan showing unadjusted lower mortality with combined ivermectin and doxycycline treatment. Details of the ivermectin group compared to other patients are not provided, however ivermectin was given to a similar percentage of patients in the mild, moderate, and severe/critical groups (34.5%, 29.1%, and 36.4%), suggesting that ivermectin treatment was not based on severity.
Apr 2021, Cureus, https://www.cureus.com/articles/56545-clinical-variants-characteristics-and-outcomes-among-covid-19-patients-a-case-series-analysis-at-a-tertiary-care-hospital-in-karachi-pakistan, https://c19p.org/ahsandox