SARS-CoV-2 InfectionPhase 2/3COVIDMEDNCT04328012
COVID MED Trial - Comparison Of Therapeutics for Hospitalized Patients Infected With COVID-19
A Phase 2/3 study testing Losartan in people with SARS-CoV-2 Infection, run by Bassett Healthcare at 1 site in United States.
Trial summary
In a randomized, double-blind, placebo-controlled, multi-center, Phase 2-like, investigator-directed trial, hospitalized adult patients with laboratory confirmed SARS-CoV-2 infection meeting inclusion and exclusion criteria, will be provided information on the trial, offered enrollment, and if informed consent… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- SARS-CoV-2 Infection
- What is being tested?
- Losartan
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Apr 2020to 1 Dec 2021
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
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
- Hospitalized patient
- Age >= 18 years
- Able to ingest oral medication or be administered medication via gastric tube or equivalent
- Laboratory confirmation of SARS-CoV-2 infection within 1 week prior to randomization
- Randomization within 72 hr of hospital admission
- Negative pregnancy test for reproductive age women
- Patient or LAR able to provide informed consent
Who cannot join
- Allergy or intolerance to losartan or other ARBs
- Already taking ACE or ARB (within 1 month)
- Hypotension at time of enrollment (SBP < 100 mm Hg)
- Hyperkalemia (K >/= 5.0 at time of screening or history of hyperkalemia)
- Severe renal dysfunction (estimated GFR < 30 ml/min at time of screening or history advanced renal disease)
- Severe volume depletion or acute kidney injury (AKI) at time of enrollment
Show all 15Show fewer
- Known cirrhotic ascites
- Known severe aortic or mitral valve stenosis
- Known unstented renal artery stenosis
- Co-administration with certain drugs due to CYP3A interactions if taken in < 24 hr
- Severe hepatic insufficiency (LFTs > 5 times the upper limit of normal or known ESLD or cirrhosis)
- Nausea/vomiting or aspiration risk precluding oral medications unless can be given by gastric tube
- Pregnancy or breast feeding
- Absence of dependable contraception in reproductive age women
- Inability to obtain or declined informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Comparison Of Therapeutics for Hospitalized Patients Infected With SARS-CoV-2 In a Pragmatic aDaptive randoMizED Clinical Trial During the COVID-19 Pandemic (COVID MED Trial)
In a randomized, double-blind, placebo-controlled, multi-center, Phase 2-like, investigator-directed trial, hospitalized adult patients with laboratory confirmed SARS-CoV-2 infection meeting inclusion and exclusion criteria, will be provided information on the trial, offered enrollment, and if informed consent provided, enrolled randomly in a 2:1 ratio to one of two groups: Group 1 standard care and losartan or Group 2 standard care and placebo. Patients will be followed for up to 60 days, with data collected to quantify the NCOSS over time (the primary objective), and for the trial's secondary objectives (see outcome measurements below).
Read the detailed description
Although a number of therapeutics have been utilized by clinicians to treat hospitalized patients with COVID-19, none were systematically evaluated in clinical trials at the time of the outset of this RCT (COVID MED). Since then, dexamethasone has been shown to decrease mortality and remdesivir to possibly decrease hospital LOS in the RECOVERY and ACTT-II trials and others. The initial iteration of this protocol included 4 arms, hydroxychloroquine, lopinavir/ritonavir, losartan, and placebo based on suggestive efficacy and safety and widespread empiric use. The current iteration of COVID MED includes two arms, standard of care and losartan vs. standard of care and placebo.
Hydroxychloroquine was initially included in COVID MED based on suggestive in vitro, animal preclinical, and early RCT data, and widespread empiric use in hospitalized patients with COVID-19. Lopinavir/ritonavir, an antiretroviral medication, showed equivocal and possibly positive efficacy and safety in an early pandemic Chinese RCT published in NEJM. After public release and eventual publication of the negative results for hydroxychloroquine and then lopinavir/ritonavir initially from the RECOVERY trial and then others, enrollment in COVID MED in these two arms was halted and then discontinued permanently. Data from subjects enrolled in the hydroxychloroquine arm are being incorporated into a pooled analysis of RCTs by the Trial Innovation Network.
Losartan, an angiotensin II receptor blocker (ARB), has theoretical benefit as SARSCoV-2 appears to bind to lung tissue via Angiotensin-Converting Enzyme 2 (ACE-2) receptors which might be inhibited by ARBs; other potential benefits have been hypothesized as well. Since the initial iteration of this protocol, observational studies have shown that patients already taking ACEi/ARB medications do not have adverse outcome when these drugs are continued in hospitalized COVID-19 patients. These data have reinforced continuation of the losartan vs. placebo arms of this RCT which are ongoing.
This pragmatic adaptive trial continues to compare outcome in hospitalized COVID-19 patients treated with standard of care and losartan vs. standard of care and placebo.
- Conditions
- SARS-CoV-2 Infection
- Being tested
- Losartan, Placebo
- Keywords
- COVID, COVID-19, coronavirus
- Medical subject headings
- COVID-19, Coronavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LosartanDrug
Also called Cozaar
administered 14 days
PlaceboDrug
administered 14 days
| Study group | Role | What they receive |
|---|---|---|
| Losartan | Experimental | losartan 25 mg po QD X 14 days Receives: Drug: Losartan |
| Placebo | Placebo comparator | placebo QD X 14 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
National Institute of Allergy and Infectious Diseases COVID-19 Ordinal Severity Scale (NCOSS)
difference in NCOSS scores between the different treatment groups
Measured: 60 days
Secondary outcomes (4)
Hospital length of stay (LOS)
difference in the total inpatient LOS between the three treatment groups
Measured: 60 days
Intensive care unit level LOS
difference in the total ICU level care LOS between the three treatment groups
Measured: 60 days
Mechanical ventilation
difference in length of use of mechanical ventilation between the three treatment groups
Measured: 60 days
survival
difference in all cause mortality between the four treatment groups
Measured: 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2020
- Study start6 Apr 2020
- Primary completion1 Jul 2021
- Study completion1 Dec 2021
Why it stopped: difficult enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SARS-CoV-2 InfectionStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomized, double blind, placebo controlled clinical trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bassett Healthcare
- Sponsor type
- University, hospital or other
- Collaborators
- Reid Health, Goshen Health System
- Responsible party
- Principal investigator, Daniel Freilich, MD, Bassett Healthcare
- Investigators
- Daniel Freilich, MD, Principal investigator, Bassett Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04328012
- Sponsor's protocol ID
- 1581969
- Acronym
- COVIDMED
- Status last verified
- Mar 2022
- First submitted
- 27 Mar 2020
- Last updated
- 24 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
PubMed 34473343
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison Of Therapeutics for Hospitalized Patients Infected With SARS-CoV-2 In a Pragmatic aDaptive randoMizED Clinical Trial During the COVID-19 Pandemic (COVID MED Trial)
- ClinicalTrials.gov ID
- NCT04328012
- Acronym / sponsor ID
- COVIDMED / 1581969
- Conditions
- SARS-CoV-2 Infection
- Keywords
- COVID, COVID-19, coronavirus
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: difficult enrollment
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Bassett HealthcareUniversity, hospital or other
- Collaborators
- Reid Health, Goshen Health System
- Study start
- 6 Apr 2020 (actual)
- Primary completion
- 1 Jul 2021 (actual)
- Study completion
- 1 Dec 2021 (actual)
- First posted
- 31 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In a randomized, double-blind, placebo-controlled, multi-center, Phase 2-like, investigator-directed trial, hospitalized adult patients with laboratory confirmed SARS-CoV-2 infection meeting inclusion and exclusion criteria, will be provided information on the trial, offered enrollment, and if informed consent provided, enrolled randomly in a 2:1 ratio to one of two groups: Group 1 standard care and losartan or Group 2 standard care and placebo. Patients will be followed for up to 60 days, with data collected to quantify the NCOSS over time (the primary objective), and for the trial's secondary objectives (see outcome measurements below).
Detailed description
Although a number of therapeutics have been utilized by clinicians to treat hospitalized patients with COVID-19, none were systematically evaluated in clinical trials at the time of the outset of this RCT (COVID MED). Since then, dexamethasone has been shown to decrease mortality and remdesivir to possibly decrease hospital LOS in the RECOVERY and ACTT-II trials and others. The initial iteration of this protocol included 4 arms, hydroxychloroquine, lopinavir/ritonavir, losartan, and placebo based on suggestive efficacy and safety and widespread empiric use. The current iteration of COVID MED includes two arms, standard of care and losartan vs. standard of care and placebo.
Hydroxychloroquine was initially included in COVID MED based on suggestive in vitro, animal preclinical, and early RCT data, and widespread empiric use in hospitalized patients with COVID-19. Lopinavir/ritonavir, an antiretroviral medication, showed equivocal and possibly positive efficacy and safety in an early pandemic Chinese RCT published in NEJM. After public release and eventual publication of the negative results for hydroxychloroquine and then lopinavir/ritonavir initially from the RECOVERY trial and then others, enrollment in COVID MED in these two arms was halted and then discontinued permanently. Data from subjects enrolled in the hydroxychloroquine arm are being incorporated into a pooled analysis of RCTs by the Trial Innovation Network.
Losartan, an angiotensin II receptor blocker (ARB), has theoretical benefit as SARSCoV-2 appears to bind to lung tissue via Angiotensin-Converting Enzyme 2 (ACE-2) receptors which might be inhibited by ARBs; other potential benefits have been hypothesized as well. Since the initial iteration of this protocol, observational studies have shown that patients already taking ACEi/ARB medications do not have adverse outcome when these drugs are continued in hospitalized COVID-19 patients. These data have reinforced continuation of the losartan vs. placebo arms of this RCT which are ongoing.
This pragmatic adaptive trial continues to compare outcome in hospitalized COVID-19 patients treated with standard of care and losartan vs. standard of care and placebo.
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, double blind, placebo controlled clinical trial
| Arm | Type | Receives |
|---|---|---|
| Losartan | Experimental | Drug: Losartanlosartan 25 mg po QD X 14 days |
| Placebo | Placebo comparator | Drug: Placeboplacebo QD X 14 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Hospitalized patient
- Age >= 18 years
- Able to ingest oral medication or be administered medication via gastric tube or equivalent
- Laboratory confirmation of SARS-CoV-2 infection within 1 week prior to randomization
- Randomization within 72 hr of hospital admission
Key exclusion criteria (15 listed)
- Allergy or intolerance to losartan or other ARBs
- Already taking ACE or ARB (within 1 month)
- Hypotension at time of enrollment (SBP < 100 mm Hg)
- Hyperkalemia (K >/= 5.0 at time of screening or history of hyperkalemia)
- Severe renal dysfunction (estimated GFR < 30 ml/min at time of screening or history advanced renal disease)
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 |
|---|---|---|
| LosartanAlso: Cozaaradministered 14 days | Drug | Losartan |
| Placeboadministered 14 days | Drug | Placebo |
Primary outcome
National Institute of Allergy and Infectious Diseases COVID-19 Ordinal Severity Scale (NCOSS)
Time frame: 60 days
difference in NCOSS scores between the different treatment groups
4 secondary outcomes
Hospital length of stay (LOS)
Time frame: 60 days
Intensive care unit level LOS
Time frame: 60 days
Mechanical ventilation
Time frame: 60 days
survival
Time frame: 60 days
Results and safety
The study was stopped early (reason given: difficult enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2022.
- Derived from this study: PubMed 34473343Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
- Individual participant dataSharing planned: No
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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.
Daniel Freilich, MD principal investigator
Bassett Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Losartan in people with SARS-CoV-2 Infection, run by Bassett Healthcare 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 7 inclusion and 15 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 24 Mar 2022. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: difficult enrollment). Results are not available in the source record.
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?
National Institute of Allergy and Infectious Diseases COVID-19 Ordinal Severity Scale (NCOSS) (time frame: 60 days). 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 NCT04328012, which also lists 1 linked publication.
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 24 Mar 2022.