Covid19Phase 2NCT04865029
Estradiol and Progesterone in Hospitalized COVID-19 Patients
A Phase 2 study testing Estradiol Cypionate 5 mg/ml and Progesterone 200 mg Oral Capsule in people with Covid19, run by Tulane University at 1 site in United States.
Trial summary
The purpose of this study is to determine to what extent a short systemic steroid therapy with estradiol and progesterone, administered early to hospitalized and confirmed COVID-19 positive patients of both sexes in addition to standard of care (SOC) can reduce the severity of symptoms and outcomes compared to SOC… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19
- What is being tested?
- Estradiol Cypionate 5 mg/ml and Progesterone 200 mg Oral Capsule
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Jul 2021to 25 Jan 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Hospitalization at Tulane Medical Center in the Department of General Internal Medicine and Geriatrics with COVID-19 (WHO Ordinal scale score 3-5) and confirmed by SARS-CoV-2 Polymerase Chain Reaction (PCR).
- Respiratory symptoms (fever, shortness of breath or cough) or abnormal lung exam or chest imaging characteristic of mild to severe COVID-19 pneumonia.
- Patient and/or legally authorized representative (LAR) agrees to comply with study procedures and the collection of blood samples per protocol.
- Patient and/or LAR agrees to be placed on prophylactic dose of anticoagulation for prevention of deep venous thrombosis (DVT) (if necessary).
- Patient or legally authorized representative has signed informed consent.
- Women of childbearing age with a negative pregnancy test on admission.
Who cannot join
- Patient under 18 years of age.
- Critical COVID-19 (respiratory failure requiring intubation and mechanical ventilation, shock, multi-organ failure).
- Pregnant women confirmed by pregnancy test.
- Women who are within six weeks of postpartum.
- Patient is not hospitalized at Tulane Medical Center with confirmed COVID-19.
- Patient included in another COVID-19 trial (excluding hydroxychloroquine and dexamethasone).
Show all 17Show fewer
- Women already treated by estrogen and or progestogen therapy two weeks prior to admission.
- Men already treated by testosterone therapy prior to admission.
- History of breast or endometrial cancer.
- Abnormal genital bleeding.
- Active or recent (e.g., within the past year) stroke or myocardial infarction.
- History of blood clots including deep vein thrombosis related to clotting disease, or pulmonary emboli (prior to hospitalization).
- History of liver dysfunction or disease.
- Patients with end-stage renal disease
- Patients taking inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, and ritonavir.
- Patients taking St. John's Wort preparations (Hypericum perforatum), phenobarbital, carbamazepine, and rifampin.
- Patients within 6 weeks of major orthopedic surgery.
Trial locations and contacts
1 site in 1 country.
United States1 site
Tulane University Medical Center
New Orleans, Louisiana, 70112
About this study
Official title: Acute Estradiol and Progesterone Therapy in Hospitalized Adults to Reduce Coronavirus Disease (COVID-19) Severity: A Randomized Control Trial
The purpose of this study is to determine to what extent a short systemic steroid therapy with estradiol and progesterone, administered early to hospitalized and confirmed COVID-19 positive patients of both sexes in addition to standard of care (SOC) can reduce the severity of symptoms and outcomes compared to SOC alone.
Read the detailed description
Severe Acute Respiratory Syndrome Associated Corona Virus (SARS-CoV-2), causing COVID-19, has killed over 2.8 million people globally, including 550,000 in the US as of March 2021. Although, the vaccination campaign is ramping up, vaccination hesitancy in the United States represents up to 25-30% of the population, and hospitalizations and deaths are still at the level of 2020. Apart from corticosteroids, most available therapeutic options are at best marginally efficient in reducing disease severity and mortality and extremely expensive. Therefore, the systematic investigation of clinically approved drugs is a priority in order to determine what does improve the disease and invest resources to go to full-scale production. Our current understanding of the disease is that COVID-19 deaths result from an inappropriate immune response with outpouring of pro-inflammatory chemokines leading to lung infiltration and hyperactivation of monocytes and macrophages producing pro-inflammatory cytokines (cytokine storm), resulting in lung edema, reduced gas exchange, and ultimately leading to acute respiratory distress syndrome and multiorgan failure. Men with COVID-19 have a uniformly more severe outcome than women. In series from China, Europe and the U.S., COVID-19 mortality was consistently 1.5 to 2-fold higher in men than in women, suggesting that female biological sex is protecting women from COVID-19 mortality. It is established that women exhibit heightened immune responses to viral infections compared to men, which is at least partially due to the genetic benefit of gene dosage in X-linked immune-response genes. Ovarian steroids, however, also play a protective role. In New York City, among 5700 hospitalized patients, the female protection from COVID-19 mortality was observed at all ages, but was more pronounced in subjects under 50 years of age (18% mortality in women) compared to patients > 50 years of age (40.5% mortality in women), suggesting that ovarian steroids are involved in mitigating COVID-19 mortality in pre-menopausal women. Further, the analysis of electronic health records of over 68,000 COVID-19 patients revealed that estrogen therapy is associated with more than 50% reduction in mortality. The main female steroids, 17β-estradiol and progesterone exhibit potent immuno-modulatory and anti-inflammatory actions via estrogen and progesterone receptors expressed in all immune cells, including epithelial cells, macrophages, dendritic cells, cluster of differentiation 4 (CD4+) and cluster of differentiation 8 (CD8+) lymphocytes, and B cells. Progesterone also acts partially via the glucocorticoid receptor. Together estradiol and progesterone produce a state of decreased innate immune cells production of proinflammatory cytokines, enhanced T cells anti-inflammatory responses and immune tolerance, and enhanced B-cell-mediated antibody production. The National Institutes of Health (NIH) COVID-19 Treatment Guidelines Panel recommends the use of dexamethasone 6 mg per day for up to 10 days or until hospital Discharge (whichever comes first) as standard of care (SOC) for the treatment of hospitalized COVID-19 patients who require supplemental oxygen but who are not mechanically ventilated and for the treatment of hospitalized patients who are mechanically ventilated. Remdesivir is SOC at Tulane for COVID-19 patients who require supplemental oxygen but who are not mechanically ventilated. We believe that in hospitalized COVID-19 patients, a short treatment with the combination estradiol and progesterone, administered early and as a prevention in addition to SOC, will prevent or mitigate the cytokine storm while increasing antibody production and prevent severe outcomes, without side effects. Therefore, it will provide steroid immunomodulation without immunosuppression. The advantage of repurposing estradiol and progesterone compounds is the depth of knowledge regarding their clinical efficacy and toxicity that has accumulated from decades of clinical and basic studies. Estradiol and progesterone are widely available in hospitals, inexpensive, manufacturable to scale, and can be prescribed immediately.
- Conditions
- Covid19
- Being tested
- Placebo injection and placebo pill, Estradiol Cypionate 5 mg/ml, Progesterone 200 mg Oral Capsule
- Keywords
- Estradiol, Progesterone, Covid19, Estrogen, Hormones, Progestogens, Depo-Estradiol, Prometrium, Micronized Progesterone
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo injection and placebo pillOther
Standard of Care consistent with the National Institutes of Health (NIH) COVID-19 Treatment Guidelines
Estradiol Cypionate 5 mg/mlDrug
Standard of Care along with Estradiol Cypionate 5mg intramuscular injection at admission.
Progesterone 200 mg Oral CapsuleDrug
Standard of Care along with Progesterone 200mg by mouth daily for 5 days starting at admission.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | Standard of Care along with Estradiol Cypionate 5mg intramuscular injection at admission and Progesterone 200mg by mouth daily for 5 days starting at admission. Receives: Drug: Estradiol Cypionate 5 mg/ml; Drug: Progesterone 200 mg Oral Capsule |
| Control Arm | Other | Standard of Care along with placebo injection and placebo pill
Standard of Care consistent with the National Institutes of Health (NIH) COVID-19 Treatment Guidelines Receives: Other: Placebo injection and placebo pill |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Scores 1 or 2 on the 9-point World Health Organization (WHO) Ordinal Scale at Discharge, Measured up to Day 21
The proportion will be calculated based on WHO ordinal scale for clinical improvement. The scale is from 0 to 8, with a higher score indicating worse clinical status.
- Uninfected: No clinical or virological evidence of infection 0
- Ambulatory: No limitation of activities 1 Limitation of activities 2
- Hospitalized Mild Disease Hospitalized, no oxygen therapy 3 Oxygen by mask or nasal prongs 4
- Hospitalized Severe Disease Non-invasive ventilation or high flow oxygen 5 Intubation and mechanical ventilation 6 Ventilation + additional organ support - 7 pressors, Renal Replacement Therapy (RRT), Extracorporeal Membrane Oxygenation (ECMO)
- Dead Death 8
Measured: At discharge, measured up to Day 21
Secondary outcomes (7)
Length of Hospital Stay
The investigators will review patients' medical records on day 14 and day 28. Then, the investigators will call patients on day 60. This will be done to determine the efficiency of treatment on length of hospital stay.
Measured: Baseline to day 60
Readmission
The investigators will review patients' medical records on day 14 and day 28. Then, the investigators will call patients on day 60. This will be done to determine the readmission rates.
Measured: Baseline to day 60
Number of Patients Requiring Invasive Mechanical Ventilation
The investigators will review patients' medical records on day 14 and day 28. Then, the investigators will call patients on day 60. This will be done to determine the number of patients requiring invasive mechanical ventilation
Measured: Baseline to day 60
Number of Days Death Occurred After Admission
The investigators will review patients' medical records on day 14 and day 28 and calculate number of deaths that occurred after admission. Then, the investigators will call patients on day 60. This will be done to determine the number of days death occurred after admission.
Measured: Baseline to day 60
Number of Participants With Each Cause of Death
The investigators will review patients' medical records on day 14 and day 28 and determine the cause of death. Then, the investigators will call patients on day 60. This will be done to determine the cause of death.
Measured: Baseline to day 60
Grade 3 Adverse Events Occurrence
Subjects will be followed daily for 7 days after initiation of treatment for adverse events. The investigators will review patients' medical records on day 14 and day 28. Then, the investigators will call patients on day 60. This will be done to determine the frequency and severity of adverse events in treatment arm vs. control arm.
Measured: Baseline to day 60
Serious Adverse Events Occurrence
Subjects will be followed daily for 7 days after initiation of treatment for serious adverse events. The investigators will review patients' medical records on day 14 and day 28. Then, the investigators will call patients on day 60. This will be done to determine the frequency of serious adverse events in treatment arm vs. control arm.
Measured: Baseline to day 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2021
- Study start22 Jul 2021
- Primary completion25 Jan 2022
- Study completion25 Jan 2022
Why it stopped: Lack of enrollment due to change of COVID 19 variant prevalence
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (29)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, placebo-controlled
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tulane University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Franck Mauvais-Jarvias, MD, PhD, Principal investigator, Tulane University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04865029
- Sponsor's protocol ID
- 2020-939
- Status last verified
- Jun 2023
- First submitted
- 21 Apr 2021
- Last updated
- 27 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. doi: 10.1016/S0140-6736(20)30628-0. Epub 2020 Mar 16. No abstract available.
PubMed 32192578Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, Wang T, Zhang X, Chen H, Yu H, Zhang X, Zhang M, Wu S, Song J, Chen T, Han M, Li S, Luo X, Zhao J, Ning Q. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020 May 1;130(5):2620-2629. doi: 10.1172/JCI137244.
PubMed 32217835Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.
PubMed 31986264Blanco-Melo D, Nilsson-Payant BE, Liu WC, Uhl S, Hoagland D, Moller R, Jordan TX, Oishi K, Panis M, Sachs D, Wang TT, Schwartz RE, Lim JK, Albrecht RA, tenOever BR. Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19. Cell. 2020 May 28;181(5):1036-1045.e9. doi: 10.1016/j.cell.2020.04.026. Epub 2020 May 15.
PubMed 32416070Chousterman BG, Swirski FK, Weber GF. Cytokine storm and sepsis disease pathogenesis. Semin Immunopathol. 2017 Jul;39(5):517-528. doi: 10.1007/s00281-017-0639-8. Epub 2017 May 29.
PubMed 28555385Ye Q, Wang B, Mao J. The pathogenesis and treatment of the ;Cytokine Storm' in COVID-19. J Infect. 2020 Jun;80(6):607-613. doi: 10.1016/j.jinf.2020.03.037. Epub 2020 Apr 10.
PubMed 32283152Tanaka T, Narazaki M, Kishimoto T. Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy. 2016 Jul;8(8):959-70. doi: 10.2217/imt-2016-0020.
PubMed 27381687McGonagle D, Sharif K, O'Regan A, Bridgewood C. The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease. Autoimmun Rev. 2020 Jun;19(6):102537. doi: 10.1016/j.autrev.2020.102537. Epub 2020 Apr 3.
PubMed 32251717Mauvais-Jarvis F, Bairey Merz N, Barnes PJ, Brinton RD, Carrero JJ, DeMeo DL, De Vries GJ, Epperson CN, Govindan R, Klein SL, Lonardo A, Maki PM, McCullough LD, Regitz-Zagrosek V, Regensteiner JG, Rubin JB, Sandberg K, Suzuki A. Sex and gender: modifiers of health, disease, and medicine. Lancet. 2020 Aug 22;396(10250):565-582. doi: 10.1016/S0140-6736(20)31561-0.
PubMed 32828189Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28.
PubMed 32109013Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW; the Northwell COVID-19 Research Consortium; Barnaby DP, Becker LB, Chelico JD, Cohen SL, Cookingham J, Coppa K, Diefenbach MA, Dominello AJ, Duer-Hefele J, Falzon L, Gitlin J, Hajizadeh N, Harvin TG, Hirschwerk DA, Kim EJ, Kozel ZM, Marrast LM, Mogavero JN, Osorio GA, Qiu M, Zanos TP. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020 May 26;323(20):2052-2059. doi: 10.1001/jama.2020.6775.
PubMed 32320003Klein SL, Dhakal S, Ursin RL, Deshpande S, Sandberg K, Mauvais-Jarvis F. Biological sex impacts COVID-19 outcomes. PLoS Pathog. 2020 Jun 22;16(6):e1008570. doi: 10.1371/journal.ppat.1008570. eCollection 2020 Jun.
PubMed 32569293Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol. 2016 Oct;16(10):626-38. doi: 10.1038/nri.2016.90. Epub 2016 Aug 22.
PubMed 27546235Phiel KL, Henderson RA, Adelman SJ, Elloso MM. Differential estrogen receptor gene expression in human peripheral blood mononuclear cell populations. Immunol Lett. 2005 Feb 15;97(1):107-13. doi: 10.1016/j.imlet.2004.10.007.
PubMed 15626482Straub RH. The complex role of estrogens in inflammation. Endocr Rev. 2007 Aug;28(5):521-74. doi: 10.1210/er.2007-0001. Epub 2007 Jul 19.
PubMed 17640948
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Estradiol and Progesterone Therapy in Hospitalized Adults to Reduce Coronavirus Disease (COVID-19) Severity: A Randomized Control Trial
- ClinicalTrials.gov ID
- NCT04865029
- Acronym / sponsor ID
- 2020-939
- Conditions
- Covid19
- Keywords
- Estradiol, Progesterone, Covid19, Estrogen, Hormones, Progestogens, Depo-Estradiol, Prometrium
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of enrollment due to change of COVID 19 variant prevalence
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Tulane UniversityUniversity, hospital or other
- Study start
- 22 Jul 2021 (actual)
- Primary completion
- 25 Jan 2022 (actual)
- Study completion
- 25 Jan 2022 (actual)
- First posted
- 29 Apr 2021 (actual)
- Results
- Posted 27 Jun 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine to what extent a short systemic steroid therapy with estradiol and progesterone, administered early to hospitalized and confirmed COVID-19 positive patients of both sexes in addition to standard of care (SOC) can reduce the severity of symptoms and outcomes compared to SOC alone.
Detailed description
Severe Acute Respiratory Syndrome Associated Corona Virus (SARS-CoV-2), causing COVID-19, has killed over 2.8 million people globally, including 550,000 in the US as of March 2021. Although, the vaccination campaign is ramping up, vaccination hesitancy in the United States represents up to 25-30% of the population, and hospitalizations and deaths are still at the level of 2020. Apart from corticosteroids, most available therapeutic options are at best marginally efficient in reducing disease severity and mortality and extremely expensive. Therefore, the systematic investigation of clinically approved drugs is a priority in order to determine what does improve the disease and invest resources to go to full-scale production. Our current understanding of the disease is that COVID-19 deaths result from an inappropriate immune response with outpouring of pro-inflammatory chemokines leading to lung infiltration and hyperactivation of monocytes and macrophages producing pro-inflammatory cytokines (cytokine storm), resulting in lung edema, reduced gas exchange, and ultimately leading to acute respiratory distress syndrome and multiorgan failure. Men with COVID-19 have a uniformly more severe outcome than women. In series from China, Europe and the U.S., COVID-19 mortality was consistently 1.5 to 2-fold higher in men than in women, suggesting that female biological sex is protecting women from COVID-19 mortality. It is established that women exhibit heightened immune responses to viral infections compared to men, which is at least partially due to the genetic benefit of gene dosage in X-linked immune-response genes. Ovarian steroids, however, also play a protective role. In New York City, among 5700 hospitalized patients, the female protection from COVID-19 mortality was observed at all ages, but was more pronounced in subjects under 50 years of age (18% mortality in women) compared to patients > 50 years of age (40.5% mortality in women), suggesting that ovarian steroids are involved in mitigating COVID-19 mortality in pre-menopausal women. Further, the analysis of electronic health records of over 68,000 COVID-19 patients revealed that estrogen therapy is associated with more than 50% reduction in mortality. The main female steroids, 17β-estradiol and progesterone exhibit potent immuno-modulatory and anti-inflammatory actions via estrogen and progesterone receptors expressed in all immune cells, including epithelial cells, macrophages, dendritic cells, cluster of differentiation 4 (CD4+) and cluster of differentiation 8 (CD8+) lymphocytes, and B cells. Progesterone also acts partially via the glucocorticoid receptor. Together estradiol and progesterone produce a state of decreased innate immune cells production of proinflammatory cytokines, enhanced T cells anti-inflammatory responses and immune tolerance, and enhanced B-cell-mediated antibody production. The National Institutes of Health (NIH) COVID-19 Treatment Guidelines Panel recommends the use of dexamethasone 6 mg per day for up to 10 days or until hospital Discharge (whichever comes first) as standard of care (SOC) for the treatment of hospitalized COVID-19 patients who require supplemental oxygen but who are not mechanically ventilated and for the treatment of hospitalized patients who are mechanically ventilated. Remdesivir is SOC at Tulane for COVID-19 patients who require supplemental oxygen but who are not mechanically ventilated. We believe that in hospitalized COVID-19 patients, a short treatment with the combination estradiol and progesterone, administered early and as a prevention in addition to SOC, will prevent or mitigate the cytokine storm while increasing antibody production and prevent severe outcomes, without side effects. Therefore, it will provide steroid immunomodulation without immunosuppression. The advantage of repurposing estradiol and progesterone compounds is the depth of knowledge regarding their clinical efficacy and toxicity that has accumulated from decades of clinical and basic studies. Estradiol and progesterone are widely available in hospitals, inexpensive, manufacturable to scale, and can be prescribed immediately.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, placebo-controlled
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Drug: Estradiol Cypionate 5 mg/ml, Drug: Progesterone 200 mg Oral CapsuleStandard of Care along with Estradiol Cypionate 5mg intramuscular injection at admission and Progesterone 200mg by mouth daily for 5 days starting at admission. |
| Control Arm | Other | Other: Placebo injection and placebo pillStandard of Care along with placebo injection and placebo pill Standard of Care consistent with the National Institutes of Health (NIH) COVID-19 Treatment Guidelines |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Hospitalization at Tulane Medical Center in the Department of General Internal Medicine and Geriatrics with COVID-19 (WHO Ordinal scale score 3-5) and confirmed by SARS-CoV-2 Polymerase Chain Reaction (PCR).
- Respiratory symptoms (fever, shortness of breath or cough) or abnormal lung exam or chest imaging characteristic of mild to severe COVID-19 pneumonia.
- Patient and/or legally authorized representative (LAR) agrees to comply with study procedures and the collection of blood samples per protocol.
- Patient and/or LAR agrees to be placed on prophylactic dose of anticoagulation for prevention of deep venous thrombosis (DVT) (if necessary).
- Patient or legally authorized representative has signed informed consent.
Key exclusion criteria (17 listed)
- Patient under 18 years of age.
- Critical COVID-19 (respiratory failure requiring intubation and mechanical ventilation, shock, multi-organ failure).
- Pregnant women confirmed by pregnancy test.
- Women who are within six weeks of postpartum.
- Patient is not hospitalized at Tulane Medical Center with confirmed COVID-19.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo injection and placebo pillStandard of Care consistent with the National Institutes of Health (NIH) COVID-19 Treatment Guidelines | Other | Control Arm |
| Estradiol Cypionate 5 mg/mlStandard of Care along with Estradiol Cypionate 5mg intramuscular injection at admission. | Drug | Treatment Arm |
| Progesterone 200 mg Oral CapsuleStandard of Care along with Progesterone 200mg by mouth daily for 5 days starting at admission. | Drug | Treatment Arm |
Primary outcome
Number of Participants With Scores 1 or 2 on the 9-point World Health Organization (WHO) Ordinal Scale at Discharge, Measured up to Day 21
Time frame: At discharge, measured up to Day 21
The proportion will be calculated based on WHO ordinal scale for clinical improvement. The scale is from 0 to 8, with a higher score indicating worse clinical status. * Uninfected: No clinical or virological evidence of infection 0 * Ambulatory: No limitation of activities 1 Limitation of activities 2 * Hospitalized Mild Disease Hospitalized, no oxygen therapy 3 Oxygen by mask or nasal prongs 4 * Hospitalized Severe Disease Non-invasive ventilation or high flow oxygen 5 Intubation and mechanical ventilation 6 Ventilation + additional organ support - 7 pressors, Renal Replacement Therapy (RRT), Extracorporeal Membrane Oxygenation (ECMO) * Dead Death 8
7 secondary outcomes
Length of Hospital Stay
Time frame: Baseline to day 60
Readmission
Time frame: Baseline to day 60
Number of Patients Requiring Invasive Mechanical Ventilation
Time frame: Baseline to day 60
Number of Days Death Occurred After Admission
Time frame: Baseline to day 60
Number of Participants With Each Cause of Death
Time frame: Baseline to day 60
Grade 3 Adverse Events Occurrence
Time frame: Baseline to day 60
Serious Adverse Events Occurrence
Time frame: Baseline to day 60
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 32192578Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. doi: 10.1016/S0140-6736(20)30628-0. Epub 2020 Mar 16. No abstract available.
- Background: PubMed 32217835Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, Wang T, Zhang X, Chen H, Yu H, Zhang X, Zhang M, Wu S, Song J, Chen T, Han M, Li S, Luo X, Zhao J, Ning Q. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020 May 1;130(5):2620-2629. doi: 10.1172/JCI137244.
- Background: PubMed 31986264Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.
- Background: PubMed 32416070Blanco-Melo D, Nilsson-Payant BE, Liu WC, Uhl S, Hoagland D, Moller R, Jordan TX, Oishi K, Panis M, Sachs D, Wang TT, Schwartz RE, Lim JK, Albrecht RA, tenOever BR. Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19. Cell. 2020 May 28;181(5):1036-1045.e9. doi: 10.1016/j.cell.2020.04.026. Epub 2020 May 15.
- Background: PubMed 28555385Chousterman BG, Swirski FK, Weber GF. Cytokine storm and sepsis disease pathogenesis. Semin Immunopathol. 2017 Jul;39(5):517-528. doi: 10.1007/s00281-017-0639-8. Epub 2017 May 29.
- Background: PubMed 32283152Ye Q, Wang B, Mao J. The pathogenesis and treatment of the ;Cytokine Storm' in COVID-19. J Infect. 2020 Jun;80(6):607-613. doi: 10.1016/j.jinf.2020.03.037. Epub 2020 Apr 10.
- Background: PubMed 27381687Tanaka T, Narazaki M, Kishimoto T. Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy. 2016 Jul;8(8):959-70. doi: 10.2217/imt-2016-0020.
- Background: PubMed 32251717McGonagle D, Sharif K, O'Regan A, Bridgewood C. The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease. Autoimmun Rev. 2020 Jun;19(6):102537. doi: 10.1016/j.autrev.2020.102537. Epub 2020 Apr 3.
- Background: PubMed 32828189Mauvais-Jarvis F, Bairey Merz N, Barnes PJ, Brinton RD, Carrero JJ, DeMeo DL, De Vries GJ, Epperson CN, Govindan R, Klein SL, Lonardo A, Maki PM, McCullough LD, Regitz-Zagrosek V, Regensteiner JG, Rubin JB, Sandberg K, Suzuki A. Sex and gender: modifiers of health, disease, and medicine. Lancet. 2020 Aug 22;396(10250):565-582. doi: 10.1016/S0140-6736(20)31561-0.
- Background: PubMed 32109013Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28.
- Background: PubMed 32320003Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW; the Northwell COVID-19 Research Consortium; Barnaby DP, Becker LB, Chelico JD, Cohen SL, Cookingham J, Coppa K, Diefenbach MA, Dominello AJ, Duer-Hefele J, Falzon L, Gitlin J, Hajizadeh N, Harvin TG, Hirschwerk DA, Kim EJ, Kozel ZM, Marrast LM, Mogavero JN, Osorio GA, Qiu M, Zanos TP. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020 May 26;323(20):2052-2059. doi: 10.1001/jama.2020.6775.
- Background: PubMed 32569293Klein SL, Dhakal S, Ursin RL, Deshpande S, Sandberg K, Mauvais-Jarvis F. Biological sex impacts COVID-19 outcomes. PLoS Pathog. 2020 Jun 22;16(6):e1008570. doi: 10.1371/journal.ppat.1008570. eCollection 2020 Jun.
- Individual participant dataSharing planned: No
Related trials for Covid19
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Active, not recruitingPhase 1
A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults
COVID-19
Active, not recruiting
Intervention to Address Disparate Mental Health Consequences of COVID-19 Pandemic on Latinx and African Newcomers
Mental Health Issue, Mental Health Disorder
Recruiting
Home-Based Exercise Tele-Rehabilitation After COVID-19
Post SARS-CoV2 (COVID-19)
Not yet recruitingPhase 1
A Safety, Reactogenicity and Immunogenicity Trial of RVX-sCPD9 Booster Intranasal COVID-19 Vaccine
COVID -19
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Franck Mauvais-Jarvias, MD, PhD principal investigator
Tulane University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Estradiol Cypionate 5 mg/ml and Progesterone 200 mg Oral Capsule in people with Covid19, run by Tulane University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Scores 1 or 2 on the 9-point World Health Organization (WHO) Ordinal Scale at Discharge, Measured up to Day 21 (time frame: At discharge, measured up to Day 21). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04865029, which also lists 29 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2023.