Virus DiseasesPhase 2ProPAC-COVIDNCT04322396

Proactive Protection With Azithromycin and hydroxyChloroquine in Hospitalized Patients With COVID-19

A Phase 2 study testing Azithromycin and Hydroxychloroquine in people with Virus Diseases and Infection Viral, run by Chronic Obstructive Pulmonary Disease Trial Network, Denmark at 8 sites in Denmark.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This study explores whether patients acutely hospitalized may have shorter hospitalization and fewer admittances at Intensive Care Units by treatment with azithromycin and hydroxychloroquine. Read more about this study

Who is it for?: Any age
Conditions the study is for: Virus Diseases, Infection Viral, Corona Virus Infection
What is being tested?: Azithromycin and Hydroxychloroquine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 117 participants
Where: 8 sitesDenmark
Study dates: 6 Apr 2020to 2 Feb 2021
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 Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Patient admitted to a Danish emergency department, lung medical department or medical department
Age >18 years
Hospitalized <48 hours
Positive COVID-19 test/diagnosis during the hospitalization
Signs informed consent

Who cannot join

If the patient uses > 5 LO2/min at time of recruitment
Known intolerance/allergy to azithromycin or hydroxychloroquine or hypersensitivity to quinine or 4-aminoquinolinderivates
Pregnancy
Breastfeeding
Neurogenic hearing loss
Psoriasis

Show all 21Show fewer

Retinopathy
Maculopathy
Changes in vision field
Severe liver disease other than amoebiases
Severe gastrointestinal, neurological or haematological disorders
eGFR < 45 ml/min/1.73m2
Clinically significant cardiac conduction disorders/arrhythmias or prolonged QTc interval
Myasthenia Gravis
Uses Digoxin
Glucose-6-phosphate dehydrogenase deficiency
Porphyria
Hypoglycemia at any time since hospitalization
Severe mental illness which significantly impedes cooperation
Severe linguistic problems that significantly impedes cooperation
Treatment with sickle alkaloids

Trial locations and contacts

8 sites in 1 country.

City, postcode or hospital

8 sites in 1 country

Denmark8 sites

Aalborg Sygehus
Aalborg
Bispebjerg Hospital
Copenhagen
Herlev-Gentofte Hospital
Copenhagen
Hvidovre Hospital
Copenhagen
Nordsjællands Hospital
Hillerød
Odense Universitetshospital
Odense
Roskilde Sygehus
Roskilde
Slagelse Sygehus
Slagelse

Other trials in Denmark

About this study

Official title: Proactive Protection With Azithromycin and Hydroxychloroquine in Hospitalized Patients With COVID: A Randomized, Placebo-controlled Double-blinded Trial Evaluating Treatment With Azithromycin and Hydroxychloroquine to Patients With COVID-19

This study explores whether patients acutely hospitalized may have shorter hospitalization and fewer admittances at Intensive Care Units by treatment with azithromycin and hydroxychloroquine.

Read the detailed description

In the ongoing coronavirus pandemic, COVID-19, that arose in Wuhan China, there is still sparse data in the course, risk of various complications, and in particular how patients who are hospitalized are best treated to ensure high survival and short hospitalization. Despite the rapid spread of the disease globally, there is no solid data yet to recommend any specific treatments, which is why symptomatic, organ supportive therapy including respiratory therapy in acute pulmonary failure is recommended. There has been reported a high incidence of bacterial super-infections in patients with COVID-19. Patients with COVID-19 also have a higher risk of dying because of septic shock. Thus, there is an urgent need for treatment that can improve the patient's chance of the shortest hospitalization possible, and treatment that can lower the risk of secondary infection and death.

This is a randomized, placebo-controlled, double-blinded multi-center trial evaluating the effect of azithromycin and hydroxychloroquine treatment in patients with COVID-19 during hospitalization. The aim of the study is to investigate whether the treatment can shorten hospitalization, reduce the risk of non-invasive ventilation, admittance to Intensive Care Units and death.

Conditions: Virus Diseases, Infection Viral, Corona Virus Infection
Being tested: Azithromycin, Hydroxychloroquine, Placebo oral tablet
Medical subject headings: Virus Diseases, Coronavirus Infections

What participants receive

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

AzithromycinDrug
Azithromycin
HydroxychloroquineDrug
Hydroxychloroquine
Placebo oral tabletDrug
Placebo Azithromycin
Placebo oral tabletDrug
Placebo Hydroxychloroquine

Study groups in NCT04322396
Study group	Role	What they receive
Control	Placebo comparator	This arm will receive standard care and placebo in 15 days. Azithromycin placebo: Day 1-3: 500 mg x 1 Day 4-15: 250 mg x 1 Hydroxychloroquine placebo: Day 1-15: 200 mg x 2 Receives: Drug: Placebo oral tablet
Intervention	Active comparator	This arm will receive standard care and azithromycin and hydroxychloroquine in 15 days. Azithromycin: Day 1-3: 500 mg x 1 Day 4-15: 250 mg x 1 Hydroxychloroquine: Day 1-15: 200 mg x 2 Receives: Drug: Azithromycin; Drug: Hydroxychloroquine

What is being measured

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

Number of Days Alive and Discharged From Hospital Within 14 Days
Measured: 14 days

Secondary outcomes (14)

Categorization of Hospitalization Status
The patient will be categorized into one of the following 8 categories depending on status of their hospitalization:
1. Dead (yes/no)
2. Hospitalized and receiving mechanical ventilation or ExtraCorporalMembraneOxygenation (ECMO) (yes/no)
3. Hospitalized and receiving Non-invasive ventilation or "high-flow oxygen device" (yes/no)
4. Hospitalized and given oxygen supplements different from (2) and (3) (yes/no)
5. Hospitalized and without oxygen treatment, but receiving other treatment (both related to COVID-19 or other) (yes/no)
6. Hospitalized for observation (yes/no)
7. Discharged from hospital with restriction of activity level (yes/no)
8. Discharged from hospital without any restrictions of activity level (yes/no)
Only one category can be "yes".
Measured: 14 days
Length of Stay in ICU
Length of stay in intensive care unit.
Measured: 14 days
Number of Participants on Non-invasive Ventilation (NIV) During Hospitalization
Measured: 14 days
Mortality
Measured: 30 days
Length of Hospitalization
Measured: 14 days
Days Alive and Discharged From Hospital
Measured: 30 days
Mortality
Measured: 90 days
Mortality
Measured: 365 days
Number of Readmissions (All Causes)
Measured: 30 days
Number of Days Using Non-invasive Ventilation (NIV)
Number of days using non-invasive ventilation (NIV) if on NIV during hospitalization.
Measured: 14 days
Change in Patient's Oxygen Partial Pressure
PaO2 measured in arterial puncture at baseline and 4 days.
Measured: 4 days
Change in Patient's Carbondioxide Partial Pressure
PaCO2 measured in arterial puncture at baseline and 4 days.
Measured: 4 days
Change of pH in Blood
pH measured in arterial puncture at baseline and 4 days.
Measured: 4 days
Time for no Oxygen Supplement (or Regular Oxygen Supplement "LTOT")
Time for no oxygen supplement (or regular oxygen supplement "LTOT") if on oxygen during admission.
Measured: 14 days

Timeline

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

6 Apr 20202 Feb 2021

First posted26 Mar 2020
Study start6 Apr 2020
Primary completion2 Feb 2021
Study completion2 Feb 2021

Why it stopped: Recommended by the DSMB

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 (2)Papers the sponsor has linked to this study.
Other trials for Virus DiseasesStudies 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
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 117 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04322396
Sponsor's protocol ID: KronLungesyg_COVID_19_protokol
Acronym: ProPAC-COVID
Status last verified: Jun 2021
First submitted: 23 Mar 2020
Last updated: 29 Jun 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

Publications

Sivapalan P, Ulrik CS, Lappere TS, Eklof JV, Shaker SB, Bodtger UCS, Browatzki A, Meyer CN, Weinreich UM, Laursen CB, Biering-Sorensen T, Knop FK, Lundgren JD, Jensen JS. Proactive prophylaxis with azithromycin and hydroxychloroquine in hospitalized patients with COVID-19 (ProPAC-COVID): a statistical analysis plan. Trials. 2020 Oct 20;21(1):867. doi: 10.1186/s13063-020-04795-0.
PubMed 33081817
Sivapalan P, Ulrik CS, Bojesen RD, Lapperre TS, Eklof JV, Hakansson KEJ, Browatzki A, Tidemansen C, Wilcke JT, Janner J, Gottlieb V, Meteran H, Porsbjerg C, Madsen BL, Moberg M, Pedersen L, Benfield TL, Lundgren JD, Knop FK, Biering-Sorensen T, Ghanizada M, Sonne TP, Bodtger UCS, Jensen SG, Rasmussen DB, Brondum E, Tupper OD, Sorensen SW, Alstrup G, Laursen CB, Moller UW, Sverrild A, Jensen JS. Proactive Prophylaxis With Azithromycin and HydroxyChloroquine in Hospitalised Patients With COVID-19 (ProPAC-COVID): A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Jun 10;21(1):513. doi: 10.1186/s13063-020-04409-9.
PubMed 32522282

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 29 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Proactive Protection With Azithromycin and Hydroxychloroquine in Hospitalized Patients With COVID: A Randomized, Placebo-controlled Double-blinded Trial Evaluating Treatment With Azithromycin and Hydroxychloroquine to Patients With COVID-19
ClinicalTrials.gov ID: NCT04322396
Acronym / sponsor ID: ProPAC-COVID / KronLungesyg_COVID_19_protokol
Conditions: Virus Diseases, Infection Viral, Corona Virus Infection
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Recommended by the DSMB
Enrolment: 117 participants (actual)
Lead sponsor: Chronic Obstructive Pulmonary Disease Trial Network, DenmarkUniversity, hospital or other
Study start: 6 Apr 2020 (actual)
Primary completion: 2 Feb 2021 (actual)
Study completion: 2 Feb 2021 (actual)
First posted: 26 Mar 2020 (actual)
Results: Posted 28 Jun 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study explores whether patients acutely hospitalized may have shorter hospitalization and fewer admittances at Intensive Care Units by treatment with azithromycin and hydroxychloroquine.

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

Arm	Type	Receives
Control	Placebo comparator	Drug: Placebo oral tabletThis arm will receive standard care and placebo in 15 days. Azithromycin placebo: Day 1-3: 500 mg x 1 Day 4-15: 250 mg x 1 Hydroxychloroquine placebo: Day 1-15: 200 mg x 2
Intervention	Active comparator	Drug: Azithromycin, Drug: HydroxychloroquineThis arm will receive standard care and azithromycin and hydroxychloroquine in 15 days. Azithromycin: Day 1-3: 500 mg x 1 Day 4-15: 250 mg x 1 Hydroxychloroquine: Day 1-15: 200 mg x 2

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (5 listed)

Patient admitted to a Danish emergency department, lung medical department or medical department
Age >18 years
Hospitalized <48 hours
Positive COVID-19 test/diagnosis during the hospitalization
Signs informed consent

Key exclusion criteria (21 listed)

If the patient uses > 5 LO2/min at time of recruitment
Known intolerance/allergy to azithromycin or hydroxychloroquine or hypersensitivity to quinine or 4-aminoquinolinderivates
Pregnancy
Breastfeeding
Neurogenic hearing loss

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
AzithromycinAzithromycin	Drug	Intervention
HydroxychloroquineHydroxychloroquine	Drug	Intervention
Placebo oral tabletPlacebo Azithromycin	Drug	Control
Placebo oral tabletPlacebo Hydroxychloroquine	Drug	Control

Primary outcome

Number of Days Alive and Discharged From Hospital Within 14 Days
Time frame: 14 days

14 secondary outcomes

Categorization of Hospitalization Status
Time frame: 14 days
Length of Stay in ICU
Time frame: 14 days
Number of Participants on Non-invasive Ventilation (NIV) During Hospitalization
Time frame: 14 days
Mortality
Time frame: 30 days
Length of Hospitalization
Time frame: 14 days
Days Alive and Discharged From Hospital
Time frame: 30 days
Mortality
Time frame: 90 days
Mortality
Time frame: 365 days
Number of Readmissions (All Causes)
Time frame: 30 days
Number of Days Using Non-invasive Ventilation (NIV)
Time frame: 14 days
Change in Patient's Oxygen Partial Pressure
Time frame: 4 days
Change in Patient's Carbondioxide Partial Pressure
Time frame: 4 days
Change of pH in Blood
Time frame: 4 days
Time for no Oxygen Supplement (or Regular Oxygen Supplement "LTOT")
Time frame: 14 days

Results and safety

Results posted to the registry on 28 Jun 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Control	56	56
Intervention	61	61

Primary outcome: Number of Days Alive and Discharged From Hospital Within 14 Days

Time frame: 14 days. Median (Inter-Quartile Range). Unit: days

Measure	Control n = 56	Intervention n = 61
Value	9 (7 to 10)	9 (3 to 11)

14 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were recorded during the period beginning when the patient received their first dose of trial medication up to and including day 15. All-Cause Mortality was assessed up to 30 days.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Control	2 of 56 (3.6%)	25 of 56 (44.6%)	2 of 56
Intervention	0 of 61 (0%)	31 of 61 (50.8%)	1 of 61

Limitations and caveats (from the sponsor): Early termination based on recommendations from the DSMB leading to small numbers of subjects analyzed.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33081817Sivapalan P, Ulrik CS, Lappere TS, Eklof JV, Shaker SB, Bodtger UCS, Browatzki A, Meyer CN, Weinreich UM, Laursen CB, Biering-Sorensen T, Knop FK, Lundgren JD, Jensen JS. Proactive prophylaxis with azithromycin and hydroxychloroquine in hospitalized patients with COVID-19 (ProPAC-COVID): a statistical analysis plan. Trials. 2020 Oct 20;21(1):867. doi: 10.1186/s13063-020-04795-0.
Derived from this study: PubMed 32522282Sivapalan P, Ulrik CS, Bojesen RD, Lapperre TS, Eklof JV, Hakansson KEJ, Browatzki A, Tidemansen C, Wilcke JT, Janner J, Gottlieb V, Meteran H, Porsbjerg C, Madsen BL, Moberg M, Pedersen L, Benfield TL, Lundgren JD, Knop FK, Biering-Sorensen T, Ghanizada M, Sonne TP, Bodtger UCS, Jensen SG, Rasmussen DB, Brondum E, Tupper OD, Sorensen SW, Alstrup G, Laursen CB, Moller UW, Sverrild A, Jensen JS. Proactive Prophylaxis With Azithromycin and HydroxyChloroquine in Hospitalised Patients With COVID-19 (ProPAC-COVID): A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Jun 10;21(1):513. doi: 10.1186/s13063-020-04409-9.

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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.

8 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 5 inclusion and 21 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 29 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Denmark. 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 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 28 Jun 2021). 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 Days Alive and Discharged From Hospital Within 14 Days (time frame: 14 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 NCT04322396, which also lists 2 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 29 Jun 2021.