Middle East Respiratory Syndrome Coronavirus (MERS-CoV)Phase 2/3MIRACLENCT02845843

MERS-CoV Infection tReated With A Combination of Lopinavir /Ritonavir and Interferon Beta-1b

A Phase 2/3 study testing Combination of Lopinavir /Ritonavir and Interferon beta-1b in people with Middle East Respiratory Syndrome Coronavirus (MERS-CoV), run by King Abdullah International Medical Research Center at 2 sites in Saudi Arabia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

This is a placebo-controlled clinical trial to assess the efficacy and safety of a combination of lopinavir/ritonavir and Interferon beta-1b in hospitalized patients with MERS. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
What is being tested?: Combination of Lopinavir /Ritonavir and Interferon beta-1b
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 95 participants
Where: 2 sitesSaudi Arabia
Study dates: Jul 2016to May 2020
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

Adult (defined as ≥18 years of age);
Laboratory confirmation of MERS-CoV infection by reverse-transcription polymerase chain reaction (RT-PCR) from any diagnostic sampling source; and
New organ dysfunction that is judged to related to MERS including: hypoxia defined as requirement of supplemental oxygen to maintain oxygen saturations >90%, hypotension (systolic blood pressure<90 mmHg) or need for vasopressor/inotropic medication, renal impairment (increase of creatinine by 50% from baseline, glomerular filtration rate reduction by >25% from baseline or urine output of <0.5 ml/kg for 6 hours - Risk stage by RIFLE criteria), neurologic (reduction of Glasgow Coma Scale by 2 or more, i.e. 13 or lower of 15 points), thrombocytopenia (<150,000 platelets/mm3) or gastrointestinal symptoms that requires hospitalization (e.g. severe nausea, vomiting, diarrhea or/and abdominal pain).

Who cannot join

Suicidal ideation based on history (contraindication to interferon (IFN)-β1b);
Known allergy or hypersensitivity reaction to lopinavir/ritonavir or to recombinant IFN-β1b, including, but not limited to, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, urticaria or angioedema;
Elevated alanine aminotransferase (ALT) >5 fold the upper limit in the hospital's laboratory;
Use of medications that are contraindicated with lopinavir/ritonavir and that cannot be replaced or stopped during the study period, such as CYP3A inhibitors;
Pregnancy - eligible and consenting female participants in childbearing age will be tested for pregnancy before enrollment in the study;
Known HIV infection, because of concerns about the development of resistance to lopinavir/ritonavir if used without combination with other anti-HIV drugs; or
Patient likely to be transferred to a non-participating hospital within 72 hours.

Trial locations and contacts

2 sites in 1 country.

Saudi Arabia2 sites

Intensive Care Unit, King Abdulaziz Medical City, National Guard Health Affairs
Riyadh, 11426
King Abdullah International Medical Research Center
Riyadh, 22490

Other trials in Saudi Arabia

About this study

Official title: MERS-CoV Infection tReated With A Combination of Lopinavir /Ritonavir and Interferon Beta-1b: a Multicenter, Placebo-controlled, Double-blind Randomized Trial

This is a placebo-controlled clinical trial to assess the efficacy and safety of a combination of lopinavir/ritonavir and Interferon beta-1b in hospitalized patients with MERS.

Read the detailed description

The aim of this study is to investigate the efficacy and safety of lopinavir /ritonavir and recombinant Interferon beta-1b combination given with optimal supportive care compared to placebo with optimal supportive care for patients with laboratory-confirmed MERS-CoV infection requiring hospital admission.

Conditions: Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
Being tested: Combination of Lopinavir /Ritonavir and Interferon beta-1b, Placebo
Keywords: Middle East Respiratory Syndrome Coronavirus, MERS-CoV, Clinical trial, Lopinavir, Ritonavir, Interferon beta

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Combination of Lopinavir /Ritonavir and Interferon beta-1bDrug
Lopinavir /Ritonavir 400mg +100 mg / ml twice daily for 14 days and Interferon beta-1b 0.25 mg subcutaneous every alternate day for 14 days
PlaceboDrug
Same characteristics as Lopinavir /Ritonavir and Interferon beta-1b to maintain blinding

Study groups in NCT02845843
Study group	Role	What they receive
Combination of Lopinavir /Ritonavir and IntErferon Beta 1B	Experimental	Lopinavir /Ritonavir 400mg +100 mg / ml twice daily for 14 days and Interferon beta-1b 0.25 mg subcutaneous every alternate day for 14 days Receives: Drug: Combination of Lopinavir /Ritonavir and Interferon beta-1b
Placebo	Placebo comparator	Same characteristics as Lopinavir /Ritonavir and Interferon beta-1b to maintain blinding Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

90-day mortality
Measured: 90-day

Secondary outcomes (10)

Organ support-free days (e.g., supplemental O2, ventilator, extracorporeal membrane oxygenation (ECMO), renal replacement and vasopressors)
Measured: 28 days
RT-PCR cycle threshold value in the lower respiratory samples
Measured: At randomization and every 3 days afterwards, until 2 consecutive samples are negative or reaching a maximum of 90 days
Sequential organ failure assessment (SOFA) scores
Measured: Days 0, 3, 7, 14, 21 and 28
ICU-free days
Measured: Number of days in which patients are not being cared for in the ICU during the first 28 days after enrollment
Length of stay in hospital
Measured: Up to one year from enrollment
Number of Patients with Adverse drug reactions related to the treatment
Measured: From enrollment to 28 day
Karnofsky Performance Scale
Measured: 90-day
ICU mortality
Measured: Up to one year from enrollment
Hospital mortality
Measured: Up to one year from enrollment
28-day mortality
Measured: 28-day

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2016May 2020

First posted27 Jul 2016 (estimated)
Study startJul 2016
Primary completionMay 2020
Study completionMay 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Middle East Respiratory Syndrome Coronavirus (MERS-CoV)Studies 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: This is a recursive two-stage group sequential multicenter placebo-controlled double-blind randomized controlled trial. The trial is initially designed to include 2 two-stage components. The first two-stage component is designed to adjust sample size and determine futility stopping, but not efficacy stopping (n=34). The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 95 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02845843
Sponsor's protocol ID: KingAbdullahIMRC
Acronym: MIRACLE
Status last verified: May 2020
First submitted: 20 Jun 2016
Last updated: 20 May 2020
Results posted: No
Data monitoring committee: Yes
Individual data sharing: Undecided

Publications

Arabi YM, Asiri AY, Assiri AM, Abdullah ML, Aljami HA, Balkhy HH, Al Jeraisy M, Mandourah Y, AlJohani S, Al Harbi S, Jokhdar HAA, Deeb AM, Memish ZA, Jose J, Ghazal S, Al Faraj S, Al Mekhlafi GA, Sherbeeni NM, Elzein FE, Hayden FG, Fowler RA, AlMutairi BM, Al-Dawood A, Alharbi NK. Heterogeneity of treatment effect of interferon-beta1b and lopinavir-ritonavir in patients with Middle East respiratory syndrome by cytokine levels. Sci Rep. 2022 Oct 28;12(1):18186. doi: 10.1038/s41598-022-22742-8.
PubMed 36307462
Arabi YM, Asiri AY, Assiri AM, Balkhy HH, Al Bshabshe A, Al Jeraisy M, Mandourah Y, Azzam MHA, Bin Eshaq AM, Al Johani S, Al Harbi S, Jokhdar HAA, Deeb AM, Memish ZA, Jose J, Ghazal S, Al Faraj S, Al Mekhlafi GA, Sherbeeni NM, Elzein FE, Al-Hameed F, Al Saedi A, Alharbi NK, Fowler RA, Hayden FG, Al-Dawood A, Abdelzaher M, Bajhmom W, AlMutairi BM, Hussein MA, Alothman A; Saudi Critical Care Trials Group. Interferon Beta-1b and Lopinavir-Ritonavir for Middle East Respiratory Syndrome. N Engl J Med. 2020 Oct 22;383(17):1645-1656. doi: 10.1056/NEJMoa2015294. Epub 2020 Oct 7.
PubMed 33026741
Arabi YM, Asiri AY, Assiri AM, Aziz Jokhdar HA, Alothman A, Balkhy HH, AlJohani S, Al Harbi S, Kojan S, Al Jeraisy M, Deeb AM, Memish ZA, Ghazal S, Al Faraj S, Al-Hameed F, AlSaedi A, Mandourah Y, Al Mekhlafi GA, Sherbeeni NM, Elzein FE, Almotairi A, Al Bshabshe A, Kharaba A, Jose J, Al Harthy A, Al Sulaiman M, Mady A, Fowler RA, Hayden FG, Al-Dawood A, Abdelzaher M, Bajhmom W, Hussein MA; and the Saudi Critical Care Trials group. Treatment of Middle East respiratory syndrome with a combination of lopinavir/ritonavir and interferon-beta1b (MIRACLE trial): statistical analysis plan for a recursive two-stage group sequential randomized controlled trial. Trials. 2020 Jan 3;21(1):8. doi: 10.1186/s13063-019-3846-x.
PubMed 31900204
Arabi YM, Alothman A, Balkhy HH, Al-Dawood A, AlJohani S, Al Harbi S, Kojan S, Al Jeraisy M, Deeb AM, Assiri AM, Al-Hameed F, AlSaedi A, Mandourah Y, Almekhlafi GA, Sherbeeni NM, Elzein FE, Memon J, Taha Y, Almotairi A, Maghrabi KA, Qushmaq I, Al Bshabshe A, Kharaba A, Shalhoub S, Jose J, Fowler RA, Hayden FG, Hussein MA; And the MIRACLE trial group. Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-beta1b (MIRACLE trial): study protocol for a randomized controlled trial. Trials. 2018 Jan 30;19(1):81. doi: 10.1186/s13063-017-2427-0.
PubMed 29382391

Study at a glance

From the registry record, last updated by the sponsor on 20 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: MERS-CoV Infection tReated With A Combination of Lopinavir /Ritonavir and Interferon Beta-1b: a Multicenter, Placebo-controlled, Double-blind Randomized Trial
ClinicalTrials.gov ID: NCT02845843
Acronym / sponsor ID: MIRACLE / KingAbdullahIMRC
Conditions: Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
Keywords: Middle East Respiratory Syndrome Coronavirus, MERS-CoV, Clinical trial, Lopinavir, Ritonavir, Interferon beta
Phase: Phase 2/3
Study type: Interventional
Recruitment status: Completed
Enrolment: 95 participants (actual)
Lead sponsor: King Abdullah International Medical Research CenterUniversity, hospital or other
Study start: Jul 2016 (actual)
Primary completion: May 2020 (actual)
Study completion: May 2020 (actual)
First posted: 27 Jul 2016 (estimated)
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.

This is a placebo-controlled clinical trial to assess the efficacy and safety of a combination of lopinavir/ritonavir and Interferon beta-1b in hospitalized patients with MERS.

Detailed description

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: This is a recursive two-stage group sequential multicenter placebo-controlled double-blind randomized controlled trial. The trial is initially designed to include 2 two-stage components. The first two-stage component is designed to adjust sample size and determine futility stopping, but not efficacy stopping (n=34). The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size.

Arm	Type	Receives
Combination of Lopinavir /Ritonavir and IntErferon Beta 1B	Experimental	Drug: Combination of Lopinavir /Ritonavir and Interferon beta-1bLopinavir /Ritonavir 400mg +100 mg / ml twice daily for 14 days and Interferon beta-1b 0.25 mg subcutaneous every alternate day for 14 days
Placebo	Placebo comparator	Drug: PlaceboSame characteristics as Lopinavir /Ritonavir and Interferon beta-1b to maintain blinding

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Adult (defined as ≥18 years of age);
Laboratory confirmation of MERS-CoV infection by reverse-transcription polymerase chain reaction (RT-PCR) from any diagnostic sampling source; and
New organ dysfunction that is judged to related to MERS including: hypoxia defined as requirement of supplemental oxygen to maintain oxygen saturations >90%, hypotension (systolic blood pressure<90 mmHg) or need for vasopressor/inotropic medication, renal impairment (increase of creatinine by 50% from baseline, glomerular filtration rate reduction by >25% from baseline or urine output of <0.5 ml/kg for 6 hours - Risk stage by RIFLE criteria), neurologic (reduction of Glasgow Coma Scale by 2 or more, i.e. 13 or lower of 15 points), thrombocytopenia (<150,000 platelets/mm3) or gastrointestinal symptoms that requires hospitalization (e.g. severe nausea, vomiting, diarrhea or/and abdominal pain).

Key exclusion criteria (7 listed)

Suicidal ideation based on history (contraindication to interferon (IFN)-β1b);
Known allergy or hypersensitivity reaction to lopinavir/ritonavir or to recombinant IFN-β1b, including, but not limited to, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, urticaria or angioedema;
Elevated alanine aminotransferase (ALT) >5 fold the upper limit in the hospital's laboratory;
Use of medications that are contraindicated with lopinavir/ritonavir and that cannot be replaced or stopped during the study period, such as CYP3A inhibitors;
Pregnancy - eligible and consenting female participants in childbearing age will be tested for pregnancy before enrollment in the study;

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
Combination of Lopinavir /Ritonavir and Interferon beta-1bLopinavir /Ritonavir 400mg +100 mg / ml twice daily for 14 days and Interferon beta-1b 0.25 mg subcutaneous every alternate day for 14 days	Drug	Combination of Lopinavir /Ritonavir and IntErferon Beta 1B
PlaceboSame characteristics as Lopinavir /Ritonavir and Interferon beta-1b to maintain blinding	Drug	Placebo

Primary outcome

90-day mortality
Time frame: 90-day

10 secondary outcomes

Organ support-free days (e.g., supplemental O2, ventilator, extracorporeal membrane oxygenation (ECMO), renal replacement and vasopressors)
Time frame: 28 days
RT-PCR cycle threshold value in the lower respiratory samples
Time frame: At randomization and every 3 days afterwards, until 2 consecutive samples are negative or reaching a maximum of 90 days
Sequential organ failure assessment (SOFA) scores
Time frame: Days 0, 3, 7, 14, 21 and 28
ICU-free days
Time frame: Number of days in which patients are not being cared for in the ICU during the first 28 days after enrollment
Length of stay in hospital
Time frame: Up to one year from enrollment
Number of Patients with Adverse drug reactions related to the treatment
Time frame: From enrollment to 28 day
Karnofsky Performance Scale
Time frame: 90-day
ICU mortality
Time frame: Up to one year from enrollment
Hospital mortality
Time frame: Up to one year from enrollment
28-day mortality
Time frame: 28-day

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2020.
Derived from this study: PubMed 36307462Arabi YM, Asiri AY, Assiri AM, Abdullah ML, Aljami HA, Balkhy HH, Al Jeraisy M, Mandourah Y, AlJohani S, Al Harbi S, Jokhdar HAA, Deeb AM, Memish ZA, Jose J, Ghazal S, Al Faraj S, Al Mekhlafi GA, Sherbeeni NM, Elzein FE, Hayden FG, Fowler RA, AlMutairi BM, Al-Dawood A, Alharbi NK. Heterogeneity of treatment effect of interferon-beta1b and lopinavir-ritonavir in patients with Middle East respiratory syndrome by cytokine levels. Sci Rep. 2022 Oct 28;12(1):18186. doi: 10.1038/s41598-022-22742-8.
Derived from this study: PubMed 33026741Arabi YM, Asiri AY, Assiri AM, Balkhy HH, Al Bshabshe A, Al Jeraisy M, Mandourah Y, Azzam MHA, Bin Eshaq AM, Al Johani S, Al Harbi S, Jokhdar HAA, Deeb AM, Memish ZA, Jose J, Ghazal S, Al Faraj S, Al Mekhlafi GA, Sherbeeni NM, Elzein FE, Al-Hameed F, Al Saedi A, Alharbi NK, Fowler RA, Hayden FG, Al-Dawood A, Abdelzaher M, Bajhmom W, AlMutairi BM, Hussein MA, Alothman A; Saudi Critical Care Trials Group. Interferon Beta-1b and Lopinavir-Ritonavir for Middle East Respiratory Syndrome. N Engl J Med. 2020 Oct 22;383(17):1645-1656. doi: 10.1056/NEJMoa2015294. Epub 2020 Oct 7.
Derived from this study: PubMed 31900204Arabi YM, Asiri AY, Assiri AM, Aziz Jokhdar HA, Alothman A, Balkhy HH, AlJohani S, Al Harbi S, Kojan S, Al Jeraisy M, Deeb AM, Memish ZA, Ghazal S, Al Faraj S, Al-Hameed F, AlSaedi A, Mandourah Y, Al Mekhlafi GA, Sherbeeni NM, Elzein FE, Almotairi A, Al Bshabshe A, Kharaba A, Jose J, Al Harthy A, Al Sulaiman M, Mady A, Fowler RA, Hayden FG, Al-Dawood A, Abdelzaher M, Bajhmom W, Hussein MA; and the Saudi Critical Care Trials group. Treatment of Middle East respiratory syndrome with a combination of lopinavir/ritonavir and interferon-beta1b (MIRACLE trial): statistical analysis plan for a recursive two-stage group sequential randomized controlled trial. Trials. 2020 Jan 3;21(1):8. doi: 10.1186/s13063-019-3846-x.
Derived from this study: PubMed 29382391Arabi YM, Alothman A, Balkhy HH, Al-Dawood A, AlJohani S, Al Harbi S, Kojan S, Al Jeraisy M, Deeb AM, Assiri AM, Al-Hameed F, AlSaedi A, Mandourah Y, Almekhlafi GA, Sherbeeni NM, Elzein FE, Memon J, Taha Y, Almotairi A, Maghrabi KA, Qushmaq I, Al Bshabshe A, Kharaba A, Shalhoub S, Jose J, Fowler RA, Hayden FG, Hussein MA; And the MIRACLE trial group. Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-beta1b (MIRACLE trial): study protocol for a randomized controlled trial. Trials. 2018 Jan 30;19(1):81. doi: 10.1186/s13063-017-2427-0.
Individual participant dataSharing planned: Undecided

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.

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 3 inclusion and 7 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: finished, as of the sponsor's last update on 20 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Saudi Arabia. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

90-day mortality (time frame: 90-day). 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 NCT02845843, which also lists 4 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 20 May 2020.