COVID-19 PneumoniaPhase 2/3NCT05255848
Nebulised Heparin in Patients With COVID-19 Pneumonia
A Phase 2/3 study testing Unfractionated heparin in people with COVID-19 Pneumonia, run by Lady Reading Hospital, Pakistan at 1 site in Pakistan.
Trial summary
While the pandemic continues to incite panic and the guideline recommendations regarding management of COVID continue to change, we have growing evidence that ARDS secondary to Covid-19 is associated with disseminated intravascular and alveolar fibrin deposition1. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19 Pneumonia
- What is being tested?
- Unfractionated heparin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- 1 sitePakistan
- Study dates
- 20 Jun 2022to 20 Oct 2022
- 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
- Age 18 year or older.
- Either gender
- Currently admitted to hospital.
- There is a PCR-positive sample for SARS-CoV-2 within the past 21 days. The sample can be a nasal or pharyngeal swab, sputum, tracheal aspirate, Broncho alveolar lavage, or another sample from the Patient
- WHO Modified ordinal clinical scale 3-5
Who cannot join
- Intubated and on mechanical ventilation, or requiring immediate intubation as per the treating clinician's assessment
- Heparin allergy or heparin-induced thrombocytopenia
- APTT >120 s, not due to anticoagulant therapy and does not correct with the administration of fresh frozen plasma
- Platelet count <20 × 109 /L
- Pulmonary bleeding or uncontrolled bleeding
- Pregnant or might be pregnant
Show all 12Show fewer
- Acute brain injury that may result in long-term disability
- Myopathy, spinal cord injury, or nerve injury or disease with a likely prolonged incapacity to breathe independently e.g. Guillain-Barre syndrome
- Treatment limitations in place (Ceiling of care), i.e. not for intubation, not for ICU admission
- Death is imminent or inevitable within 24 h
- Clinician objection
- Refusal to consent
Trial locations and contacts
1 site in 1 country.
Zafar Iqbal, MBBS, FCPS contact
Pakistan1 site
Pulmonology Department, Lady Reading Hospital, Peshawar
Peshawar, Khyber Pakhtunkhwa, 25000
Muhammad Imran, FCPS, 03339457550, m.imran@lrh.edu.pk
About this study
Official title: Role of Nebulized Heparin in Non-severe and Severe Covid-19 Patients Admitted to COVID Complex LRH, MTI: A Randomized Controlled Trial
While the pandemic continues to incite panic and the guideline recommendations regarding management of COVID continue to change, we have growing evidence that ARDS secondary to Covid-19 is associated with disseminated intravascular and alveolar fibrin deposition1. Strategies devised to reduce mucous and fibrin plugs will greatly help in preventing patients from progressing to invasive ventilation2 which if happens will obviously overburden the compromised intensive care facilities. Offering heparin in nebulized form has greatly reduced levels of coagulation activation in the lungs both in animal studies and in patients with acute lung injury3. As Heparin prevents further fibrin deposition but is ineffective in the removal of pre-existing fibrin plug, so early use of heparin during the course of the disease may help in limiting the complications of ARDS and hence reducing the burden faced by our intensive care units.
A prospective randomized controlled trial will be carried out in patients admitted to COVID complex to see its effects on disease progression and its role in preventing patients from progressing to require Invasive Mechanical Ventilation while being administered through local route rather than systemic. Moreover, it will also give insight and way forward regarding the improvement in the survival and earlier discharge
Read the detailed description
Second-year into the deadly COVID-19 pandemic and humanity continues to get affected/infected. The world has seen a total cases of 99.7 M, a death toll of 2.14 M, and counting4. To date, Pakistan has received more than a million cases with a death count of over twenty-five thousand5. In a country like Pakistan, the burden on intensive care is substantial. So any intervention, before the patient lands in critical care units will greatly decrease the workload on the already saturated intensive care.
While the developed world has launched mass vaccination, the masses in developing countries are yet to be vaccinated. Despite the fact that vaccines have been launched in the developed world but their widespread availability in developing countries is still ambiguous6. The disease will continue to affect a larger population in the days to come so the search for new therapeutic agents must not cease. It is a fact that protective lung ventilation with low tidal volumes decreases mortality, off-label use of effective therapeutic agents that can decrease the progression to ARDS will be greatly beneficial7. There is growing evidence that ARDS secondary to Covid-19 is associated with disseminated intravascular and alveolar fibrin deposition8. Strategies to reduce mucous and fibrin plugs will greatly help patients. Nebulization of heparin may offer benefits over systemic administration because nebulization enhances delivery to the bronchial tree and the alveolar sacs and hence reduces the potential for systemic bleeding associated with intravenous administration. Moreover, heparin in nebulized form has greatly reduced levels of coagulation activation in the lungs both in animal studies and in patients with acute lung injury. As Heparin prevents further fibrin deposition but is ineffective in the removal of pre-existing fibrin plug, so early use of heparin during the course of the disease may help in limiting the complications of ARDS. Furthermore, it will also reduce the burden of patients in intensive care units. In this study, we will conduct a randomized controlled trial to see the effects of heparin in non-severe and severe COVID-19 patients to prevent progression to invasive mechanical ventilation or death.
- Conditions
- COVID-19 Pneumonia
- Being tested
- Unfractionated heparin
- Keywords
- COVID-19, Nebulised Heparin, ARDS, Intubation, Mortality
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Unfractionated heparinDrug
Patients will be given the same standard of care treatment plus nebulized heparin 5000IU every 8 hours started 24 hours after randomization, using a compressed air nebulizer, and will be continued for one week. In case of any complication, if the attending physician feels it necessary intervention treatment will be stopped
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | Heparin sodium will be administered as a nebulised aerosol dose of 5000 IU heparin three times a day (TDS) via an ai compressor nebuliser plus standard of care treatment Receives: Drug: Unfractionated heparin |
| No Intervention | No intervention | Participants assigned to 'standard care' will receive the standard care required as determined by the treating team and will not be treated with nebulised heparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients requiring Intubation
The primary outcome is number of patients Invasive Mechanical Ventilation (Endotracheal Intubation)or death, for patients who died before intubation
Measured: 28 days
Secondary outcomes (3)
Mortality
Survival to day 28 and Survival to hospital discharge, censored at day 28
Measured: 28 Days
Oxygenation
Daily ratio of oxygen saturation by pulse oximetry to the fraction of inspired oxygen (SpO2/FiO2 ratio, highest and lowest levels)
Measured: 28 days
Number of patients showing worsening or improvement on the modified WHO ordinal scale.
This is 8 points scale, starting from zero. Where 0 means uninfected and 8 means death.
Measured: Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2022
- Study start20 Jun 2022 (estimated)
- Primary completion20 Aug 2022 (estimated)
- Study completion20 Oct 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for COVID-19 PneumoniaStudies 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
- Single group
- Masking
- None (open label)
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lady Reading Hospital, Pakistan
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Muhammad Imran, Lady Reading Hospital, Pakistan
- Investigators
- Zafar Iqbal, FCPS, Study chair, MTI, Lady Reading Hospital, Peshawar
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05255848
- Sponsor's protocol ID
- 294/LRH/MTI
- Status last verified
- Apr 2022
- First submitted
- 16 Feb 2022
- Last updated
- 26 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Planned international meta-trial see NCT04635241
Publications
Lio KU, Rali P. Coagulopathy in COVID-19. Lung India. 2021 Mar;38(Supplement):S53-S57. doi: 10.4103/lungindia.lungindia_226_20.
PubMed 33686980van Haren FMP, Richardson A, Yoon HJ, Artigas A, Laffey JG, Dixon B, Smith R, Vilaseca AB, Barbera RA, Ismail TI, Mahrous RS, Badr M, De Nucci G, Sverdloff C, van Loon LM, Camprubi-Rimblas M, Cosgrave DW, Smoot TL, Staas S, Sann K, Sas C, Belani A, Hillman C, Shute J, Carroll M, Wilkinson T, Carroll M, Singh D, Page C. INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP): Protocol and statistical analysis plan for an investigator-initiated international metatrial of randomised studies. Br J Clin Pharmacol. 2021 Aug;87(8):3075-3091. doi: 10.1111/bcp.14714. Epub 2021 Jan 19.
PubMed 33377218Imran M, Khan S, Khan S, Uddin A, Khan MS, Ambade P. COVID-19 situation in Pakistan: A broad overview. Respirology. 2021 Sep;26(9):891-892. doi: 10.1111/resp.14093. Epub 2021 May 31. No abstract available.
PubMed 34056791Stilma W, Schultz MJ, Paulus F. Preventing mucus plugging in invasively ventilated intensive care unit patients-routine or personalized care and 'primum non nocere'. J Thorac Dis. 2018 Dec;10(12):E817-E818. doi: 10.21037/jtd.2018.11.128. No abstract available.
PubMed 30746263Chimenti L, Camprubi-Rimblas M, Guillamat-Prats R, Gomez MN, Tijero J, Blanch L, Artigas A. Nebulized Heparin Attenuates Pulmonary Coagulopathy and Inflammation through Alveolar Macrophages in a Rat Model of Acute Lung Injury. Thromb Haemost. 2017 Nov;117(11):2125-2134. doi: 10.1160/TH17-05-0347. Epub 2017 Nov 30.
PubMed 29202212Home - Johns Hopkins Coronavirus Resource Center. Johns Hopkins Coronavirus Resource Center 2021
Villar J, Blanco J, Anon JM, Santos-Bouza A, Blanch L, Ambros A, Gandia F, Carriedo D, Mosteiro F, Basaldua S, Fernandez RL, Kacmarek RM; ALIEN Network. The ALIEN study: incidence and outcome of acute respiratory distress syndrome in the era of lung protective ventilation. Intensive Care Med. 2011 Dec;37(12):1932-41. doi: 10.1007/s00134-011-2380-4. Epub 2011 Oct 14.
PubMed 21997128
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Nebulized Heparin in Non-severe and Severe Covid-19 Patients Admitted to COVID Complex LRH, MTI: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05255848
- Acronym / sponsor ID
- 294/LRH/MTI
- Conditions
- COVID-19 Pneumonia
- Keywords
- COVID-19, Nebulised Heparin, ARDS, Intubation, Mortality
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- Lady Reading Hospital, PakistanOther government
- Study start
- 20 Jun 2022 (estimated)
- Primary completion
- 20 Aug 2022 (estimated)
- Study completion
- 20 Oct 2022 (estimated)
- First posted
- 25 Feb 2022 (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.
While the pandemic continues to incite panic and the guideline recommendations regarding management of COVID continue to change, we have growing evidence that ARDS secondary to Covid-19 is associated with disseminated intravascular and alveolar fibrin deposition1. Strategies devised to reduce mucous and fibrin plugs will greatly help in preventing patients from progressing to invasive ventilation2 which if happens will obviously overburden the compromised intensive care facilities. Offering heparin in nebulized form has greatly reduced levels of coagulation activation in the lungs both in animal studies and in patients with acute lung injury3. As Heparin prevents further fibrin deposition but is ineffective in the removal of pre-existing fibrin plug, so early use of heparin during the course of the disease may help in limiting the complications of ARDS and hence reducing the burden faced by our intensive care units.
A prospective randomized controlled trial will be carried out in patients admitted to COVID complex to see its effects on disease progression and its role in preventing patients from progressing to require Invasive Mechanical Ventilation while being administered through local route rather than systemic. Moreover, it will also give insight and way forward regarding the improvement in the survival and earlier discharge
Detailed description
Second-year into the deadly COVID-19 pandemic and humanity continues to get affected/infected. The world has seen a total cases of 99.7 M, a death toll of 2.14 M, and counting4. To date, Pakistan has received more than a million cases with a death count of over twenty-five thousand5. In a country like Pakistan, the burden on intensive care is substantial. So any intervention, before the patient lands in critical care units will greatly decrease the workload on the already saturated intensive care.
While the developed world has launched mass vaccination, the masses in developing countries are yet to be vaccinated. Despite the fact that vaccines have been launched in the developed world but their widespread availability in developing countries is still ambiguous6. The disease will continue to affect a larger population in the days to come so the search for new therapeutic agents must not cease. It is a fact that protective lung ventilation with low tidal volumes decreases mortality, off-label use of effective therapeutic agents that can decrease the progression to ARDS will be greatly beneficial7. There is growing evidence that ARDS secondary to Covid-19 is associated with disseminated intravascular and alveolar fibrin deposition8. Strategies to reduce mucous and fibrin plugs will greatly help patients. Nebulization of heparin may offer benefits over systemic administration because nebulization enhances delivery to the bronchial tree and the alveolar sacs and hence reduces the potential for systemic bleeding associated with intravenous administration. Moreover, heparin in nebulized form has greatly reduced levels of coagulation activation in the lungs both in animal studies and in patients with acute lung injury. As Heparin prevents further fibrin deposition but is ineffective in the removal of pre-existing fibrin plug, so early use of heparin during the course of the disease may help in limiting the complications of ARDS. Furthermore, it will also reduce the burden of patients in intensive care units. In this study, we will conduct a randomized controlled trial to see the effects of heparin in non-severe and severe COVID-19 patients to prevent progression to invasive mechanical ventilation or death.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Drug: Unfractionated heparinHeparin sodium will be administered as a nebulised aerosol dose of 5000 IU heparin three times a day (TDS) via an ai compressor nebuliser plus standard of care treatment |
| No Intervention | No intervention | –Participants assigned to 'standard care' will receive the standard care required as determined by the treating team and will not be treated with nebulised heparin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age 18 year or older.
- Either gender
- Currently admitted to hospital.
- There is a PCR-positive sample for SARS-CoV-2 within the past 21 days. The sample can be a nasal or pharyngeal swab, sputum, tracheal aspirate, Broncho alveolar lavage, or another sample from the Patient
- WHO Modified ordinal clinical scale 3-5
Key exclusion criteria (12 listed)
- Intubated and on mechanical ventilation, or requiring immediate intubation as per the treating clinician's assessment
- Heparin allergy or heparin-induced thrombocytopenia
- APTT >120 s, not due to anticoagulant therapy and does not correct with the administration of fresh frozen plasma
- Platelet count <20 × 109 /L
- Pulmonary bleeding or uncontrolled bleeding
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 |
|---|---|---|
| Unfractionated heparinPatients will be given the same standard of care treatment plus nebulized heparin 5000IU every 8 hours started 24 hours after randomization, using a compressed air nebulizer, and will be continued for one week. In case of any complication, if the attending physician feels it necessary intervention treatment will be stopped | Drug | Intervention |
Primary outcome
Number of patients requiring Intubation
Time frame: 28 days
The primary outcome is number of patients Invasive Mechanical Ventilation (Endotracheal Intubation)or death, for patients who died before intubation
3 secondary outcomes
Mortality
Time frame: 28 Days
Oxygenation
Time frame: 28 days
Number of patients showing worsening or improvement on the modified WHO ordinal scale.
Time frame: Day 7
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2022.
- Background: PubMed 33686980Lio KU, Rali P. Coagulopathy in COVID-19. Lung India. 2021 Mar;38(Supplement):S53-S57. doi: 10.4103/lungindia.lungindia_226_20.
- Background: PubMed 33377218van Haren FMP, Richardson A, Yoon HJ, Artigas A, Laffey JG, Dixon B, Smith R, Vilaseca AB, Barbera RA, Ismail TI, Mahrous RS, Badr M, De Nucci G, Sverdloff C, van Loon LM, Camprubi-Rimblas M, Cosgrave DW, Smoot TL, Staas S, Sann K, Sas C, Belani A, Hillman C, Shute J, Carroll M, Wilkinson T, Carroll M, Singh D, Page C. INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP): Protocol and statistical analysis plan for an investigator-initiated international metatrial of randomised studies. Br J Clin Pharmacol. 2021 Aug;87(8):3075-3091. doi: 10.1111/bcp.14714. Epub 2021 Jan 19.
- Background: PubMed 34056791Imran M, Khan S, Khan S, Uddin A, Khan MS, Ambade P. COVID-19 situation in Pakistan: A broad overview. Respirology. 2021 Sep;26(9):891-892. doi: 10.1111/resp.14093. Epub 2021 May 31. No abstract available.
- Background: PubMed 30746263Stilma W, Schultz MJ, Paulus F. Preventing mucus plugging in invasively ventilated intensive care unit patients-routine or personalized care and 'primum non nocere'. J Thorac Dis. 2018 Dec;10(12):E817-E818. doi: 10.21037/jtd.2018.11.128. No abstract available.
- Background: PubMed 29202212Chimenti L, Camprubi-Rimblas M, Guillamat-Prats R, Gomez MN, Tijero J, Blanch L, Artigas A. Nebulized Heparin Attenuates Pulmonary Coagulopathy and Inflammation through Alveolar Macrophages in a Rat Model of Acute Lung Injury. Thromb Haemost. 2017 Nov;117(11):2125-2134. doi: 10.1160/TH17-05-0347. Epub 2017 Nov 30.
- BackgroundHome - Johns Hopkins Coronavirus Resource Center. Johns Hopkins Coronavirus Resource Center 2021
- Background: PubMed 21997128Villar J, Blanco J, Anon JM, Santos-Bouza A, Blanch L, Ambros A, Gandia F, Carriedo D, Mosteiro F, Basaldua S, Fernandez RL, Kacmarek RM; ALIEN Network. The ALIEN study: incidence and outcome of acute respiratory distress syndrome in the era of lung protective ventilation. Intensive Care Med. 2011 Dec;37(12):1932-41. doi: 10.1007/s00134-011-2380-4. Epub 2011 Oct 14.
- Individual participant dataSharing planned: Yes. Planned international meta-trial see NCT04635241
Related trials for COVID-19 Pneumonia
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Active, not recruitingPhase 1
A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults
COVID-19
Recruiting
Home-Based Exercise Tele-Rehabilitation After COVID-19
Post SARS-CoV2 (COVID-19)
Not yet recruitingPhase 1
A Safety, Reactogenicity and Immunogenicity Trial of RVX-sCPD9 Booster Intranasal COVID-19 Vaccine
COVID -19
RecruitingObservational study
Cardiovascular Disease Progression in Survivors of Community Acquired Pneumonia and Lung Infection by Covid-19.
Pneumonia, Community-Acquired, COVID-19 Pneumonia
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.
Zafar Iqbal, MBBS, FCPS contact
Zafar Iqbal, FCPS study chair
MTI, Lady Reading Hospital, Peshawar
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 Unfractionated heparin in people with COVID-19 Pneumonia, run by Lady Reading Hospital, Pakistan at 1 site in Pakistan.
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 12 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: status not confirmed, as of the sponsor's last update on 26 Apr 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 Pakistan. 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.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Muhammad Imran, MBBS, FCPS (0092333945755, m.imran@lrh.edu.pk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients requiring Intubation (time frame: 28 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 NCT05255848, which also lists 7 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 26 Apr 2022.