- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04374903
Hydroxychloroquine in Combination With Sirolimus and Dexamethasone for Treating COVID-19 Patients (COVID19-HOPE)
May 25, 2022 updated by: Iyad Sultan, King Hussein Cancer Center
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).
Study Overview
Study Type
Interventional
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Amman, Jordan
- King Hussein Cancer Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Study Arm A (HCQ & AZ)
Subjects will receive HCQ 600mg PO X 10 days and AZ PO 250mg DAILY X 10 days.
|
Subjects will receive either Hydroxychloroquine with Azithromycin or Hydroxychloroquine with Sirolimus
Other Names:
|
EXPERIMENTAL: 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
|
Subjects will receive either Hydroxychloroquine with Azithromycin or Hydroxychloroquine with Sirolimus
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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).
|
28 Days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical failure defined as death or need for Intubation and mechanical ventilation
Time Frame: 28 Days
|
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).
|
28 Days
|
Adverse effects
Time Frame: 28 Days
|
Safety and tolerability, as assessed by the occurrence of adverse events in any of the study arms.
|
28 Days
|
QT interval prolongation
Time Frame: 28 Days
|
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.
|
28 Days
|
Failure to continue assigned therapy
Time Frame: 28 Days
|
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.
|
28 Days
|
Time to viral clearance
Time Frame: 28 Days
|
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.
|
28 Days
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
April 1, 2022
Primary Completion (ACTUAL)
April 1, 2022
Study Completion (ACTUAL)
April 1, 2022
Study Registration Dates
First Submitted
May 3, 2020
First Submitted That Met QC Criteria
May 3, 2020
First Posted (ACTUAL)
May 5, 2020
Study Record Updates
Last Update Posted (ACTUAL)
May 27, 2022
Last Update Submitted That Met QC Criteria
May 25, 2022
Last Verified
May 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Coronavirus Infections
- Coronaviridae Infections
- Nidovirales Infections
- RNA Virus Infections
- Virus Diseases
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Pneumonia, Viral
- Pneumonia
- Lung Diseases
- COVID-19
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antifungal Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Sirolimus
- Azithromycin
- Hydroxychloroquine
Other Study ID Numbers
- 20 KHCC 74
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on COVID-19 Patients
-
Daewoong Pharmaceutical Co. LTD.Novotech (Australia) Pty LimitedUnknown
-
Saglik Bilimleri UniversitesiRecruitingCovid-19 Positivity Confirmed With PCR Positivity in the Nasopharyngeal Swab | Symptomatic Covid -19 Positive Patients Who Require Hospitalization | Patients Who Did Not Vaccinate Against Covid-19 | Patients Among 20 to 90 Years of Age | Healthy Control Patients of the Same AgeTurkey
-
Beijing 302 HospitalRecruitingCOVID-19 | Vaccine Reaction | Patients With CancerChina
-
Assiut UniversityRecruiting
-
Sher-E-Bangla Medical CollegeRecruitingTo Assess Long-term Effects of COVID-19 in Patients Who Were Affected With COVID -19Bangladesh
-
Assiut UniversityNot yet recruitingCOVID-19 Infection in Hemodialysis Patients
-
Zhaohui TongRecruitingCOVID-19 PatientsChina
-
Centre Hospitalier Universitaire de NiceUnknownCovid-19 PatientsFrance
-
Sohag UniversityNot yet recruiting
-
University Hospital of FerraraUniversità degli Studi di FerraraCompletedCOVID-19 PatientsItaly
Clinical Trials on HCQ & AZ vs HCQ+SIR
-
King Hussein Cancer CenterWithdrawn
-
Novartis PharmaceuticalsCompleted
-
UnitedHealth GroupUniversity of Pennsylvania; ProHealth Care AssociatesTerminatedCorona Virus Infection | CoronavirusUnited States
-
UNICEFPak Emirates Military Hospital Rawalpindi, PakistanCompletedCovid19 | ProgressionPakistan
-
Guang'anmen Hospital of China Academy of Chinese...Unknown
-
National Institute of Allergy and Infectious Diseases...Autoimmunity Centers of ExcellenceTerminatedHealthy Participants | Rheumatoid Arthritis (RA) PreventionUnited States
-
Abramson Cancer Center of the University of PennsylvaniaTerminated
-
Postgraduate Institute of Medical Education and...Completed
-
Hospital Israelita Albert EinsteinHospital do Coracao; Hospital Sirio-Libanes; Brazilian Research In Intensive... and other collaboratorsCompletedCoronavirus Infections | Pneumonia, ViralBrazil
-
University of Sao Paulo General HospitalFundação de Amparo à Pesquisa do Estado de São PauloCompletedSystemic Lupus Erythematosus (SLE) | Cutaneous Lupus | Juvenile SLEBrazil