COVID-19 PatientsCOVID19-HOPENCT04374903
Hydroxychloroquine in Combination With Sirolimus and Dexamethasone for Treating COVID-19 Patients
A study testing HCQ & AZ vs HCQ+SIR in people with COVID-19 Patients, run by King Hussein Cancer Center at 1 site in Jordan.
Trial summary
COVID-19 caused an unprecedented international crisis. There is an urgent need for an effective regimen to cure this illness. Anecdotal data and some prospective results suggested a role of antimalarial drugs (chloroquine and hydroxychloroquine) in the treatment of this disease with best available data showing value… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19 Patients
- What is being tested?
- HCQ & AZ vs HCQ+SIR
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteJordan
- Study dates
- 1 Apr 2022to 1 Apr 2022
- Phase
- Interventional
- 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
- Male and non-pregnant female patients 18 years of age or older
- Positive RT-PCR for SARS-CoV-2.
- Fever (oral T≥39 C within 24 hours of enrollment), Tachypnea (resting respiratory rate ≥ 28/min) and/or Oxygen saturation (Sao2) ≤ 93% on room air.
- Ability to read, understand and sign IRB approved informed consent
- Patients on HCQ or HCQ/AZ already are eligible for randomization.
Who cannot join
- Weight < 40 kg.
- Pregnant (positive β-human chorionic gonadotropin test, β-HCG) or lactating female at the screening.
- Subjects with a history of retinopathy, sickle cell disease or trait, psoriasis, porphyria, history of splenectomy, mental illness or uncontrolled seizures disorder, liver cirrhosis, end-stage renal disease or need for renal replacement therapy, Decompensated heart failure, known active tuberculosis or history of incompletely treated tuberculosis, uncontrolled systemic bacterial or fungal infections, active viral infection other than COVID-19, Patients on chronic immunosuppression for other medical conditions such as rheumatological disorders, inflammatory bowel disease, or in patients with organ transplants.
- Allergy to any of the study medications.
- Drug-Drug interaction (after consulting with study PI). For example:
- Drugs that may interact and alter HCQ level: ampicillin, cimetidine, digoxin, statins, cyclosporine, warfarin, fluconazole, within 2 weeks of dosing start, and during the duration of the study.
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- Drugs that may interact and alter SIR level: rifampicin, azole antifungals, phenytoin, diltiazem, verapamil, nicardipine, phenobarbital, carbamazepine, within 2 weeks of dosing start, and during the duration of the study.
- Any abnormal baseline laboratory screening tests listed below (Exceptions by study PI may apply if reason explained)
- Liver Child-Pugh grade C (table is included in the study)
- Creatinine >1.5 mg/dl.
- Hemoglobin for males <12 g/dl and females <10 g/dl.
- Platelet count of <100 X 103/L.
- Cardiac assessment:
- Patients with baseline corrected QT >450 msec.
- Patients with decompensated heart failure or acute myocardial infarction within the past 30 days of infection.
- Patients with HypoKalemia (<3.5 mg/dl), HypoCalcemia (<8.0 mg/dl), HypoMagnesemia (<1.6mg/dl) will be included after correction.
- Advanced respiratory support (high flow oxygen ≥ 15 L/min, CPAP, non-invasive or invasive mechanical ventilation)
- Any other significant finding based on the judgment of the PI would increase the risk of having an adverse outcome from participating in this study.
- Patients that lack decision-making capacity will not be approached to participate in this study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Hydroxychloroquine in Combination With Sirolimus and Dexamethasone for Treating COVID-19 PatiEnts: A Pilot, Multicenter Randomized Open-Label Trial
COVID-19 caused an unprecedented international crisis. There is an urgent need for an effective regimen to cure this illness. Anecdotal data and some prospective results suggested a role of antimalarial drugs (chloroquine and hydroxychloroquine) in the treatment of this disease with best available data showing value of adding azithromycin. Based on drug repurposing studies done by our team and others, we identified the autophagy/apoptosis pathway as a major target for intervention. Based on in-silico and in-vitro models, sirolimus was identified as the drug that deserves urgent prioritization. The rational for combining sirolimus and hydroxychloroquine is explained in details in the study background below and a short video prepared by study PI (https://youtu.be/-zlOMXJp2hg). The evidence for using sirolimus for influenza is emphasized by a RCT that showed reduction of mechanical ventilation time by 50% (7 days on sirolimus arm vs 15 days on oseltamivir/steroids arm). Safe administration in human subjects is illustrated by multiple phase I/II clinical trials, performed in patients with cancer. COVID19-HOPE trial will randomize patients to 2 arms: HCQ/AZ (Arm A) and HCQ/SIR (Arm B). The main inclusion criteria is an RT-PCR test confirming infection with SARS-CoV-2 along with objective clinical criteria of disease (fever, tachypnea and/or hypoxemia). The primary endpoint of study will be Time To Clinical Improvement (TTCI), defined as time from randomization to resolution of the clinical features mentioned above (no fever, no tachypnea and no hypoxemia). In addition, secondary endpoints will include clinical failure by day 28 (need for intubation and/or death), QT interval prolongation, and adverse events. The estimated NNT based on Wilcoxon Mann Whitney comparison of TTCI in study arms is 58 patients (29 each arm). The study includes an adaptive plan, meaning that after different time points the study results will be evaluated and the NNT and randomization scheme (1:1 vs. others) will be evaluated and submitted to the IRB. Also, if one arm proves to be of no value, another regimen might be introduced based on available data. The study will recruit patients for a year and once approved by IRB and JFDA attempts to recruit other centers will be made (including national and regional centers).
- Conditions
- COVID-19 Patients
- Being tested
- HCQ & AZ vs HCQ+SIR
- Keywords
- COVID-19, Hydroxychloroquine, Sirolimus, Azithromycin, HOPE
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HCQ & AZ vs HCQ+SIRDrug
Also called Hydroxychloroquine+Azithromycin, Hydroxychloroquine+Sirolimus
Subjects will receive either Hydroxychloroquine with Azithromycin or Hydroxychloroquine with Sirolimus
| Study group | Role | What they receive |
|---|---|---|
| Study Arm A (HCQ & AZ) | Experimental | Subjects will receive HCQ 600mg PO X 10 days and AZ PO 250mg DAILY X 10 days. Receives: Drug: HCQ & AZ vs HCQ+SIR |
| Study Arm B (HCQ+SIR) | Experimental | Subjects will receive HCQ 600mg PO X 10 days and SIR 4mg PO X 1 day then 2mg PO DAILY X 9 days Receives: Drug: HCQ & AZ vs HCQ+SIR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Clinical improvement (TTCI)
Time to clinical improvement (TTCI), defined as time from randomization to clinical improvement, defined as resolution of fever (oral T<38), respiratory rate(<24/min) and normalization of oxygen saturation (persistent pO2 ≥95% on RA). Assessment of clinical improvement should be confirmed on 2 consecutive days in patients who do not develop clinical failure. This outcome will be analyzed separately from clinical failure (i.e. patients with clinical failure will be excluded from TTCI calculation).
Measured: 28 Days
Secondary outcomes (5)
Clinical failure defined as death or need for Intubation and mechanical ventilation
Proportion of patients who develop clinical failure, defined as death or need for mechanical ventilation within 28 days of enrollment or until discharge (whichever later).
Measured: 28 Days
Adverse effects
Safety and tolerability, as assessed by the occurrence of adverse events in any of the study arms.
Measured: 28 Days
QT interval prolongation
Any clinically significant increase of QT, defined as increased to over 500, or increase by 60 msec (putting the patient in over 450 msec). Proportion of patients with clinically significant increase will be used as an Outcome.
Measured: 28 Days
Failure to continue assigned therapy
Proportion of patients who do not continue on assigned therapy will be calculated. Causes of failure to continue (drop-out) will be captured as well.
Measured: 28 Days
Time to viral clearance
Viral RT-PCR will be performed per institutional guidelines. The time from randomization to first negative test (Which is not followed by a positive test) will be recorded.
Measured: 28 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2020
- Study start1 Apr 2022
- Primary completion1 Apr 2022
- Study completion1 Apr 2022
Why it stopped: study could not be implemented at the site
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19 PatientsStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Subjects who are enrolled in the study will be randomly assigned to any of the study arms, A or B Study Arm A (HCQ \& AZ): Subjects will receive HCQ 600mg PO X 10 days and AZ PO 250mg DAILY X 10 days. Study Arm B (HCQ+SIR): Subjects will receive HCQ 600mg PO X 10 days and SIR 4mg PO X 1 day then 2mg PO DAILY X 9 days
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- King Hussein Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Iyad Sultan, King Hussein Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04374903
- Sponsor's protocol ID
- 20 KHCC 74
- Acronym
- COVID19-HOPE
- Status last verified
- May 2022
- First submitted
- 3 May 2020
- Last updated
- 27 May 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hydroxychloroquine in Combination With Sirolimus and Dexamethasone for Treating COVID-19 PatiEnts: A Pilot, Multicenter Randomized Open-Label Trial
- ClinicalTrials.gov ID
- NCT04374903
- Acronym / sponsor ID
- COVID19-HOPE / 20 KHCC 74
- Conditions
- COVID-19 Patients
- Keywords
- COVID-19, Hydroxychloroquine, Sirolimus, Azithromycin, HOPE
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: study could not be implemented at the site
- Enrolment
- 0 participants (actual)
- Lead sponsor
- King Hussein Cancer CenterUniversity, hospital or other
- Study start
- 1 Apr 2022 (actual)
- Primary completion
- 1 Apr 2022 (actual)
- Study completion
- 1 Apr 2022 (actual)
- First posted
- 5 May 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.
COVID-19 caused an unprecedented international crisis. There is an urgent need for an effective regimen to cure this illness. Anecdotal data and some prospective results suggested a role of antimalarial drugs (chloroquine and hydroxychloroquine) in the treatment of this disease with best available data showing value of adding azithromycin. Based on drug repurposing studies done by our team and others, we identified the autophagy/apoptosis pathway as a major target for intervention. Based on in-silico and in-vitro models, sirolimus was identified as the drug that deserves urgent prioritization. The rational for combining sirolimus and hydroxychloroquine is explained in details in the study background below and a short video prepared by study PI (https://youtu.be/-zlOMXJp2hg). The evidence for using sirolimus for influenza is emphasized by a RCT that showed reduction of mechanical ventilation time by 50% (7 days on sirolimus arm vs 15 days on oseltamivir/steroids arm). Safe administration in human subjects is illustrated by multiple phase I/II clinical trials, performed in patients with cancer. COVID19-HOPE trial will randomize patients to 2 arms: HCQ/AZ (Arm A) and HCQ/SIR (Arm B). The main inclusion criteria is an RT-PCR test confirming infection with SARS-CoV-2 along with objective clinical criteria of disease (fever, tachypnea and/or hypoxemia). The primary endpoint of study will be Time To Clinical Improvement (TTCI), defined as time from randomization to resolution of the clinical features mentioned above (no fever, no tachypnea and no hypoxemia). In addition, secondary endpoints will include clinical failure by day 28 (need for intubation and/or death), QT interval prolongation, and adverse events. The estimated NNT based on Wilcoxon Mann Whitney comparison of TTCI in study arms is 58 patients (29 each arm). The study includes an adaptive plan, meaning that after different time points the study results will be evaluated and the NNT and randomization scheme (1:1 vs. others) will be evaluated and submitted to the IRB. Also, if one arm proves to be of no value, another regimen might be introduced based on available data. The study will recruit patients for a year and once approved by IRB and JFDA attempts to recruit other centers will be made (including national and regional centers).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Subjects who are enrolled in the study will be randomly assigned to any of the study arms, A or B Study Arm A (HCQ \& AZ): Subjects will receive HCQ 600mg PO X 10 days and AZ PO 250mg DAILY X 10 days. Study Arm B (HCQ+SIR): Subjects will receive HCQ 600mg PO X 10 days and SIR 4mg PO X 1 day then 2mg PO DAILY X 9 days
| Arm | Type | Receives |
|---|---|---|
| Study Arm A (HCQ & AZ) | Experimental | Drug: HCQ & AZ vs HCQ+SIRSubjects will receive HCQ 600mg PO X 10 days and AZ PO 250mg DAILY X 10 days. |
| Study Arm B (HCQ+SIR) | Experimental | Drug: HCQ & AZ vs HCQ+SIRSubjects will receive HCQ 600mg PO X 10 days and SIR 4mg PO X 1 day then 2mg PO DAILY X 9 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male and non-pregnant female patients 18 years of age or older
- Positive RT-PCR for SARS-CoV-2.
- Fever (oral T≥39 C within 24 hours of enrollment), Tachypnea (resting respiratory rate ≥ 28/min) and/or Oxygen saturation (Sao2) ≤ 93% on room air.
- Ability to read, understand and sign IRB approved informed consent
- Patients on HCQ or HCQ/AZ already are eligible for randomization.
Key exclusion criteria (19 listed)
- Weight < 40 kg.
- Pregnant (positive β-human chorionic gonadotropin test, β-HCG) or lactating female at the screening.
- Subjects with a history of retinopathy, sickle cell disease or trait, psoriasis, porphyria, history of splenectomy, mental illness or uncontrolled seizures disorder, liver cirrhosis, end-stage renal disease or need for renal replacement therapy, Decompensated heart failure, known active tuberculosis or history of incompletely treated tuberculosis, uncontrolled systemic bacterial or fungal infections, active viral infection other than COVID-19, Patients on chronic immunosuppression for other medical conditions such as rheumatological disorders, inflammatory bowel disease, or in patients with organ transplants.
- Allergy to any of the study medications.
- Drug-Drug interaction (after consulting with study PI). For example:
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 |
|---|---|---|
| HCQ & AZ vs HCQ+SIRAlso: Hydroxychloroquine+Azithromycin, Hydroxychloroquine+SirolimusSubjects will receive either Hydroxychloroquine with Azithromycin or Hydroxychloroquine with Sirolimus | Drug | Study Arm A (HCQ & AZ), Study Arm B (HCQ+SIR) |
Primary outcome
Time to Clinical improvement (TTCI)
Time frame: 28 Days
Time to clinical improvement (TTCI), defined as time from randomization to clinical improvement, defined as resolution of fever (oral T<38), respiratory rate(<24/min) and normalization of oxygen saturation (persistent pO2 ≥95% on RA). Assessment of clinical improvement should be confirmed on 2 consecutive days in patients who do not develop clinical failure. This outcome will be analyzed separately from clinical failure (i.e. patients with clinical failure will be excluded from TTCI calculation).
5 secondary outcomes
Clinical failure defined as death or need for Intubation and mechanical ventilation
Time frame: 28 Days
Adverse effects
Time frame: 28 Days
QT interval prolongation
Time frame: 28 Days
Failure to continue assigned therapy
Time frame: 28 Days
Time to viral clearance
Time frame: 28 Days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2022.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing HCQ & AZ vs HCQ+SIR in people with COVID-19 Patients, run by King Hussein Cancer Center at 1 site in Jordan.
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 5 inclusion and 19 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: withdrawn, as of the sponsor's last update on 27 May 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 Jordan. 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.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Time to Clinical improvement (TTCI) (time frame: 28 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 May 2022.