Covid19Phase 3INSPIRATIONNCT04486508
Intermediate-dose vs Standard Prophylactic Anticoagulation and Statin vs Placebo in ICU Patients With COVID-19
A Phase 3 study testing intermediate dose Enoxaparin/ unfractionated heparin, standard prophylactic dose Enoxaparin/ unfractionated heparin and Atorvastatin 20mg in people with Covid19, run by Rajaie Cardiovascular Medical and Research Center at 1 site in Iran.
Trial summary
In a 2x2 factorial design randomized controlled trial, the investigators aim to elaborate the safety and efficacy of two pharmacological regimens on outcomes of critically-ill patients with COVID-19. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19
- What is being tested?
- intermediate dose Enoxaparin/ unfractionated heparin, standard prophylactic dose Enoxaparin/ unfractionated heparin and Atorvastatin 20mg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 600 participants
- Where
- 1 siteIran
- Study dates
- 30 Jul 2020to 5 Jul 2021
- Phase
- Phase 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 patients (≥18 years), with polymerase chain reaction (PCR)-confirmed COVID-19 admitted to ICU within 7 days of initial hospitalization , who do not have another firm indication for anticoagulation (such as mechanical valve, high-risk atrial fibrillation (AF), VTE, or left ventricle (LV) thrombus),who are not enrolled in another blinded randomized trial, and are willing to participate in the study and provide informed consent .
- Estimated survival of at least 24 hours at the discretion of enrolling physician
- Patients enrolled for the anticoagulation randomization
- Willingness to participation in the study and providing informed consent
- Exclusions Criteria for the Statin Randomization
- Baseline liver function tests> 3 times upper normal limits (ULN) or creatine kinase (CK) >500 U/L
Show all 9Show fewer
- Active liver disease (LFT>3 ULN plus histologic finding including cirrhosis or inflammation or necrosis)
- Routine use of statins prior to the index hospitalization
- Previous documented statin intolerance
Who cannot join
- Weight <40 Kilogram (kg)
- Overt bleeding at the day of enrollment
- Known major bleeding within 30 days (according to the Bleeding Academic Research Consortium (BARC) definition, Appendix A)
- Platelet count <50,000/Fl
- Pregnancy (as confirmed by Beta human chorionic gonadotropin (HCG) testing among female patients <50 years)
- Patients on Extracorporeal Membrane Oxygenation (ECMO)
Show all 16Show fewer
- History of heparin induced thrombocytopenia or immune thrombocytopenia
- Ischemic stroke within the past 2 weeks
- Craniotomy/major neurosurgery within the past 3 months
- Major head or spinal trauma in the past 30 days
- Known brain metastases or vascular malformations (aneurysm)
- Presence of an epidural, spinal or pericardial catheter
- Major surgery other than neurosurgery within 14 days prior to enrollment
- Coexistence of severe obesity (weight >120 kg or BMI>35 kg/m2 along with severe renal insufficiency defined as creatinine clearance (CrCl) <30 mL/sec)
- Allergic reaction to study medications
- Lack or withdrawal of informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Intermediate-dose Versus Standard Prophylactic Anticoagulation In cRitically-ill pATIents With COVID-19: An opeN Label Randomized Controlled Trial---A Randomized Trial of Atorvastatin vs. Placebo In Critically-ill Patients With COVID-19
In a 2x2 factorial design randomized controlled trial, the investigators aim to elaborate the safety and efficacy of two pharmacological regimens on outcomes of critically-ill patients with COVID-19. The first randomization entails open-label assignment to intermediate versus standard dose prophylactic anticoagulation. The investigators hypothesize that intermediate dose compared with standard prophylactic dose anticoagulation will have a superior efficacy with respect to a composite of venous thromboembolism (VTE), requirement for extracorporeal membrane oxygenation (ECMO), or all-cause mortality. The second randomization will be double-blind assignment of the included patients to atorvastatin 20mg daily versus matching placebo. The hypothesis is that statin therapy, compared with placebo, will reduce the composite of VTE, need for ECMO, or all-cause mortality.
Read the detailed description
Coronavirus disease-2019 (COVID-19) -- a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) -- has important manifestations outside the pulmonary parenchyma, including microthrombosis and macrothrombosis, with venous thrombosis being the most common form of thrombotic involvement. Existing studies, depending on the type of outcome assessment and type and dose of prophylaxis, have reported thrombotic events in 7-85% of patients with COVID-19.
However, the optimal antithrombotic regimen in these patients remains uncertain. Although many clinicians continue to consider standard-dose prophylactic anticoagulation, other believe that more intense anticoagulation may reduce the thrombotic events, and improve outcomes. However, limited high-quality data exist to inform clinical practice and the existing guidelines recommendations are mostly based on expert opinion and consensus.
In addition, exuberant inflammatory response is known to play a role in the pathophysiology of acute respiratory distress syndrome (ARDS) and COVID-19. It is possible that the pleiotropic effects of statins, which include anti-inflammatory and antithrombotic effects, prove beneficial in patients with severe COVID-19.
This study plans to investigate the safety and efficacy of two pharmacological regimens on outcomes of critically-ill patients with COVID-19 using a 2x2 factorial design.
First, patients will be assessed for the eligibility criteria for the anticoagulation hypothesis. Those meeting the criteria, will be assigned to intermediate versus standard dose prophylactic anticoagulation. These patients will subsequently be assessed for eligibility for the second randomization, and if meeting the criteria, will be assigned to atorvastatin 20mg/d or matching placebo.
- Conditions
- Covid19
- Being tested
- intermediate dose Enoxaparin/ unfractionated heparin, standard prophylactic dose Enoxaparin/ unfractionated heparin, Atorvastatin 20mg, Matched placebo
- Keywords
- anticoagulation, statin
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
intermediate dose Enoxaparin/ unfractionated heparinDrug
Also called Intermediate dose anticoagulation
Intermediate dose anticoagulation according to creatinine clearance and weight
standard prophylactic dose Enoxaparin/ unfractionated heparinDrug
Also called Standard dose prophylaxis anticoagulation
Standard prophylaxis anticoagulation according to creatinine clearance and weight
Atorvastatin 20mgDrug
Also called Statin
Statin
Matched placeboDrug
Also called Statin
Matched placebo to atorvastatin 20 mg
| Study group | Role | What they receive |
|---|---|---|
| Intermediate dose anticoagulation | Experimental | Intermediate dose anticoagulation will be the the tested regimen. The anticoagulation regimen will be modified according to weight/ body mass index, and creatinine clearance level (Cl Cr). Enoxaparin will be the primary agent for anticoagulation, with unfractionated heparin reserved only for patients with creatinine clearance of ≤15 mL/min according to Cockcroft-Gault Formula. Receives: Drug: intermediate dose Enoxaparin/ unfractionated heparin |
| Standard Prophylaxis | Active comparator | Standard prophylaxis dose anticoagulation will be the anticoagulation of choice in the control arm. Enoxaparin will be the primary agent for anticoagulation, with unfractionated heparin reserved only for patients with creatinine clearance of ≤15 mL/min according Cockcroft-Gault Formula. Receives: Drug: standard prophylactic dose Enoxaparin/ unfractionated heparin |
| Atorvastatin 20 | Experimental | Atorvastatin 20 mg daily will be the statin therapy of choice in the intervention arm Receives: Drug: Atorvastatin 20mg |
| Atorvastatin 20 mg Matched placebo | Placebo comparator | Matching placebo will be used for the control arm Receives: Drug: Matched placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
a composite of acute VTE, arterial thrombosis, treatment with ECMO, or all-cause mortality
composite of adjudicated 30-day acute VTE, arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause mortality.
Measured: 30 days from enrollment
Secondary outcomes (9)
Rate of all-cause mortality
Patient status regarding to being alive or dead at the end of 30-day follow up
Measured: 30 days from enrollment
Rate of objectively-confirmed VTE
Distal or proximal deep vein thrombosis which has been confirmed by ultrasonography or venography/ PE confirmed by at least one CTPA or lung scan
Measured: 30 days from enrollment
Ventilator free days
Difference between days of ICU stay and days on invasive mechanical ventilation
Measured: 30 days from enrollment
Rate of major bleeding
According to the Bleeding Academic Research Consortium (BARC 3 or 5 bleeding)
Measured: 30 days from enrollment
Rate of clinically-relevant non-major bleeding
Clinically-significant bleeding, not fulfilling criteria for major bleeding)
Measured: 30 days from enrollment
Rate of severe thrombocytopenia
Platelet count <20.000
Measured: 30 days from enrollment
Rate of rise in liver enzymes
Increase liver function tests 3 times greater than upper limit of normal
Measured: 30 days from enrollment
Clinically-diagnosed myopathy
Assessed by clinical and biomarker tests according to the treating physicians.
Measured: 30 days from enrollment
Objectively-confirmed arterial thrombosis
Imaging confirmed acute arterial thrombosis (by ultrasonography, CT, MRI, or invasive angiography)
Measured: 30 days from enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2020
- Study start30 Jul 2020
- Primary completion4 Apr 2021
- Study completion5 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- 1:1 multicenter open-label 2x2 factorial design randomized controlled trial with allocation sequence concealment and blinded endpoint adjudication.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 600 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rajaie Cardiovascular Medical and Research Center
- Sponsor type
- University, hospital or other
- Collaborators
- Brigham and Women's Hospital, Tehran Heart Center, Masih Daneshvari Hospital, Hazrat Rasool Hospital, Modarres Hospital, Firuzgar hospital affiliated to Iran University of Medical Sciences, Imam Khomeini Hospital, Sina Hospital, Iran, Tabriz University of Medical Sciences, Shariati Hospital, Imam Ali Hospital, Labbafinejhad Hospital
- Responsible party
- Principal investigator, Parham Sadeghipour, Rajaie Cardiovascular Medical and Research Center
- Investigators
- Parham Sadeghipour, MD, Principal investigator, Rajaie Cardiovascular Medical and Research CenterBehnood Bikdeli, MD, MS, Principal investigator, Brigham and Women's Hospital, Harvard Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04486508
- Sponsor's protocol ID
- 99060
- Acronym
- INSPIRATION
- Status last verified
- Aug 2021
- First submitted
- 22 Jul 2020
- Last updated
- 17 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bikdeli B, Talasaz AH, Rashidi F, Sharif-Kashani B, Farrokhpour M, Bakhshandeh H, Sezavar H, Dabbagh A, Beigmohammadi MT, Payandemehr P, Yadollahzadeh M, Riahi T, Khalili H, Jamalkhani S, Rezaeifar P, Abedini A, Lookzadeh S, Shahmirzaei S, Tahamtan O, Matin S, Amin A, Parhizgar SE, Jimenez D, Gupta A, Madhavan MV, Parikh SA, Monreal M, Hadavand N, Hajighasemi A, Maleki M, Sadeghian S, Mohebbi B, Piazza G, Kirtane AJ, Lip GYH, Krumholz HM, Goldhaber SZ, Sadeghipour P. Intermediate versus standard-dose prophylactic anticoagulation and statin therapy versus placebo in critically-ill patients with COVID-19: Rationale and design of the INSPIRATION/INSPIRATION-S studies. Thromb Res. 2020 Dec;196:382-394. doi: 10.1016/j.thromres.2020.09.027. Epub 2020 Sep 24.
PubMed 32992075Talasaz AH, Sadeghipour P, Bakhshandeh H, Sharif-Kashani B, Rashidi F, Beigmohammadi MT, Moghadam KG, Rezaian S, Dabbagh A, Sezavar SH, Farrokhpour M, Abedini A, Aliannejad R, Riahi T, Yadollahzadeh M, Lookzadeh S, Rezaeifar P, Matin S, Tahamtan O, Mohammadi K, Zoghi E, Rahmani H, Hosseini SH, Mousavian SM, Abri H, Sadeghipour P, Baghizadeh E, Rafiee F, Jamalkhani S, Amin A, Mohebbi B, Parhizgar SE, Soleimanzadeh M, Aghakouchakzadeh M, Eslami V, Payandemehr P, Khalili H, Talakoob H, Tojari T, Shafaghi S, Tabrizi S, Kakavand H, Kashefizadeh A, Najafi A, Jimenez D, Gupta A, Madhavan MV, Sethi SS, Parikh SA, Monreal M, Hadavand N, Hajighasemi A, Ansarin K, Maleki M, Sadeghian S, Barco S, Siegerink B, Spatz ES, Piazza G, Kirtane AJ, Tassell BWV, Lip GYH, Klok FA, Goldhaber SZ, Stone GW, Krumholz HM, Bikdeli B. Atorvastatin versus Placebo in ICU Patients with COVID-19: Ninety-day Results of the INSPIRATION-S Trial. Thromb Haemost. 2023 Jul;123(7):723-733. doi: 10.1055/a-2059-4844. Epub 2023 Mar 21.
PubMed 36944357Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19: a rapid review. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.
PubMed 35244208Erdem S, Ipek F, Bars A, Genc V, Erpek E, Mohammadi S, Altinata A, Akar S. Investigating the effect of macro-scale estimators on worldwide COVID-19 occurrence and mortality through regression analysis using online country-based data sources. BMJ Open. 2022 Feb 14;12(2):e055562. doi: 10.1136/bmjopen-2021-055562.
PubMed 35165110INSPIRATION-S Investigators. Atorvastatin versus placebo in patients with covid-19 in intensive care: randomized controlled trial. BMJ. 2022 Jan 7;376:e068407. doi: 10.1136/bmj-2021-068407.
PubMed 34996756INSPIRATION Investigators; Sadeghipour P, Talasaz AH, Rashidi F, Sharif-Kashani B, Beigmohammadi MT, Farrokhpour M, Sezavar SH, Payandemehr P, Dabbagh A, Moghadam KG, Jamalkhani S, Khalili H, Yadollahzadeh M, Riahi T, Rezaeifar P, Tahamtan O, Matin S, Abedini A, Lookzadeh S, Rahmani H, Zoghi E, Mohammadi K, Sadeghipour P, Abri H, Tabrizi S, Mousavian SM, Shahmirzaei S, Bakhshandeh H, Amin A, Rafiee F, Baghizadeh E, Mohebbi B, Parhizgar SE, Aliannejad R, Eslami V, Kashefizadeh A, Kakavand H, Hosseini SH, Shafaghi S, Ghazi SF, Najafi A, Jimenez D, Gupta A, Madhavan MV, Sethi SS, Parikh SA, Monreal M, Hadavand N, Hajighasemi A, Maleki M, Sadeghian S, Piazza G, Kirtane AJ, Van Tassell BW, Dobesh PP, Stone GW, Lip GYH, Krumholz HM, Goldhaber SZ, Bikdeli B. Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial. JAMA. 2021 Apr 27;325(16):1620-1630. doi: 10.1001/jama.2021.4152.
PubMed 33734299
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intermediate-dose Versus Standard Prophylactic Anticoagulation In cRitically-ill pATIents With COVID-19: An opeN Label Randomized Controlled Trial---A Randomized Trial of Atorvastatin vs. Placebo In Critically-ill Patients With COVID-19
- ClinicalTrials.gov ID
- NCT04486508
- Acronym / sponsor ID
- INSPIRATION / 99060
- Conditions
- Covid19
- Keywords
- anticoagulation, statin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 600 participants (actual)
- Lead sponsor
- Rajaie Cardiovascular Medical and Research CenterUniversity, hospital or other
- Collaborators
- Brigham and Women's Hospital, Tehran Heart Center, Masih Daneshvari Hospital, Hazrat Rasool Hospital, Modarres Hospital, Firuzgar hospital affiliated to Iran University of Medical Sciences, Imam Khomeini Hospital, Sina Hospital, Iran, Tabriz University of Medical Sciences, Shariati Hospital, Imam Ali Hospital, Labbafinejhad Hospital
- Study start
- 30 Jul 2020 (actual)
- Primary completion
- 4 Apr 2021 (actual)
- Study completion
- 5 Jul 2021 (actual)
- First posted
- 24 Jul 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.
In a 2x2 factorial design randomized controlled trial, the investigators aim to elaborate the safety and efficacy of two pharmacological regimens on outcomes of critically-ill patients with COVID-19. The first randomization entails open-label assignment to intermediate versus standard dose prophylactic anticoagulation. The investigators hypothesize that intermediate dose compared with standard prophylactic dose anticoagulation will have a superior efficacy with respect to a composite of venous thromboembolism (VTE), requirement for extracorporeal membrane oxygenation (ECMO), or all-cause mortality. The second randomization will be double-blind assignment of the included patients to atorvastatin 20mg daily versus matching placebo. The hypothesis is that statin therapy, compared with placebo, will reduce the composite of VTE, need for ECMO, or all-cause mortality.
Detailed description
Coronavirus disease-2019 (COVID-19) -- a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) -- has important manifestations outside the pulmonary parenchyma, including microthrombosis and macrothrombosis, with venous thrombosis being the most common form of thrombotic involvement. Existing studies, depending on the type of outcome assessment and type and dose of prophylaxis, have reported thrombotic events in 7-85% of patients with COVID-19.
However, the optimal antithrombotic regimen in these patients remains uncertain. Although many clinicians continue to consider standard-dose prophylactic anticoagulation, other believe that more intense anticoagulation may reduce the thrombotic events, and improve outcomes. However, limited high-quality data exist to inform clinical practice and the existing guidelines recommendations are mostly based on expert opinion and consensus.
In addition, exuberant inflammatory response is known to play a role in the pathophysiology of acute respiratory distress syndrome (ARDS) and COVID-19. It is possible that the pleiotropic effects of statins, which include anti-inflammatory and antithrombotic effects, prove beneficial in patients with severe COVID-19.
This study plans to investigate the safety and efficacy of two pharmacological regimens on outcomes of critically-ill patients with COVID-19 using a 2x2 factorial design.
First, patients will be assessed for the eligibility criteria for the anticoagulation hypothesis. Those meeting the criteria, will be assigned to intermediate versus standard dose prophylactic anticoagulation. These patients will subsequently be assessed for eligibility for the second randomization, and if meeting the criteria, will be assigned to atorvastatin 20mg/d or matching placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
- Model description
- 1:1 multicenter open-label 2x2 factorial design randomized controlled trial with allocation sequence concealment and blinded endpoint adjudication.
| Arm | Type | Receives |
|---|---|---|
| Intermediate dose anticoagulation | Experimental | Drug: intermediate dose Enoxaparin/ unfractionated heparinIntermediate dose anticoagulation will be the the tested regimen. The anticoagulation regimen will be modified according to weight/ body mass index, and creatinine clearance level (Cl Cr). Enoxaparin will be the primary agent for anticoagulation, with unfractionated heparin reserved only for patients with creatinine clearance of ≤15 mL/min according to Cockcroft-Gault Formula. |
| Standard Prophylaxis | Active comparator | Drug: standard prophylactic dose Enoxaparin/ unfractionated heparinStandard prophylaxis dose anticoagulation will be the anticoagulation of choice in the control arm. Enoxaparin will be the primary agent for anticoagulation, with unfractionated heparin reserved only for patients with creatinine clearance of ≤15 mL/min according Cockcroft-Gault Formula. |
| Atorvastatin 20 | Experimental | Drug: Atorvastatin 20mgAtorvastatin 20 mg daily will be the statin therapy of choice in the intervention arm |
| Atorvastatin 20 mg Matched placebo | Placebo comparator | Drug: Matched placeboMatching placebo will be used for the control arm |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Adult patients (≥18 years), with polymerase chain reaction (PCR)-confirmed COVID-19 admitted to ICU within 7 days of initial hospitalization , who do not have another firm indication for anticoagulation (such as mechanical valve, high-risk atrial fibrillation (AF), VTE, or left ventricle (LV) thrombus),who are not enrolled in another blinded randomized trial, and are willing to participate in the study and provide informed consent .
- Estimated survival of at least 24 hours at the discretion of enrolling physician
- Patients enrolled for the anticoagulation randomization
- Willingness to participation in the study and providing informed consent
- Exclusions Criteria for the Statin Randomization
Key exclusion criteria (16 listed)
- Weight <40 Kilogram (kg)
- Overt bleeding at the day of enrollment
- Known major bleeding within 30 days (according to the Bleeding Academic Research Consortium (BARC) definition, Appendix A)
- Platelet count <50,000/Fl
- Pregnancy (as confirmed by Beta human chorionic gonadotropin (HCG) testing among female patients <50 years)
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 |
|---|---|---|
| intermediate dose Enoxaparin/ unfractionated heparinAlso: Intermediate dose anticoagulationIntermediate dose anticoagulation according to creatinine clearance and weight | Drug | Intermediate dose anticoagulation |
| standard prophylactic dose Enoxaparin/ unfractionated heparinAlso: Standard dose prophylaxis anticoagulationStandard prophylaxis anticoagulation according to creatinine clearance and weight | Drug | Standard Prophylaxis |
| Atorvastatin 20mgAlso: StatinStatin | Drug | Atorvastatin 20 |
| Matched placeboAlso: StatinMatched placebo to atorvastatin 20 mg | Drug | Atorvastatin 20 mg Matched placebo |
Primary outcome
a composite of acute VTE, arterial thrombosis, treatment with ECMO, or all-cause mortality
Time frame: 30 days from enrollment
composite of adjudicated 30-day acute VTE, arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause mortality.
9 secondary outcomes
Rate of all-cause mortality
Time frame: 30 days from enrollment
Rate of objectively-confirmed VTE
Time frame: 30 days from enrollment
Ventilator free days
Time frame: 30 days from enrollment
Rate of major bleeding
Time frame: 30 days from enrollment
Rate of clinically-relevant non-major bleeding
Time frame: 30 days from enrollment
Rate of severe thrombocytopenia
Time frame: 30 days from enrollment
Rate of rise in liver enzymes
Time frame: 30 days from enrollment
Clinically-diagnosed myopathy
Time frame: 30 days from enrollment
Objectively-confirmed arterial thrombosis
Time frame: 30 days from enrollment
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 17 Aug 2021.
- Results publication: PubMed 32992075Bikdeli B, Talasaz AH, Rashidi F, Sharif-Kashani B, Farrokhpour M, Bakhshandeh H, Sezavar H, Dabbagh A, Beigmohammadi MT, Payandemehr P, Yadollahzadeh M, Riahi T, Khalili H, Jamalkhani S, Rezaeifar P, Abedini A, Lookzadeh S, Shahmirzaei S, Tahamtan O, Matin S, Amin A, Parhizgar SE, Jimenez D, Gupta A, Madhavan MV, Parikh SA, Monreal M, Hadavand N, Hajighasemi A, Maleki M, Sadeghian S, Mohebbi B, Piazza G, Kirtane AJ, Lip GYH, Krumholz HM, Goldhaber SZ, Sadeghipour P. Intermediate versus standard-dose prophylactic anticoagulation and statin therapy versus placebo in critically-ill patients with COVID-19: Rationale and design of the INSPIRATION/INSPIRATION-S studies. Thromb Res. 2020 Dec;196:382-394. doi: 10.1016/j.thromres.2020.09.027. Epub 2020 Sep 24.
- Derived from this study: PubMed 36944357Talasaz AH, Sadeghipour P, Bakhshandeh H, Sharif-Kashani B, Rashidi F, Beigmohammadi MT, Moghadam KG, Rezaian S, Dabbagh A, Sezavar SH, Farrokhpour M, Abedini A, Aliannejad R, Riahi T, Yadollahzadeh M, Lookzadeh S, Rezaeifar P, Matin S, Tahamtan O, Mohammadi K, Zoghi E, Rahmani H, Hosseini SH, Mousavian SM, Abri H, Sadeghipour P, Baghizadeh E, Rafiee F, Jamalkhani S, Amin A, Mohebbi B, Parhizgar SE, Soleimanzadeh M, Aghakouchakzadeh M, Eslami V, Payandemehr P, Khalili H, Talakoob H, Tojari T, Shafaghi S, Tabrizi S, Kakavand H, Kashefizadeh A, Najafi A, Jimenez D, Gupta A, Madhavan MV, Sethi SS, Parikh SA, Monreal M, Hadavand N, Hajighasemi A, Ansarin K, Maleki M, Sadeghian S, Barco S, Siegerink B, Spatz ES, Piazza G, Kirtane AJ, Tassell BWV, Lip GYH, Klok FA, Goldhaber SZ, Stone GW, Krumholz HM, Bikdeli B. Atorvastatin versus Placebo in ICU Patients with COVID-19: Ninety-day Results of the INSPIRATION-S Trial. Thromb Haemost. 2023 Jul;123(7):723-733. doi: 10.1055/a-2059-4844. Epub 2023 Mar 21.
- Derived from this study: PubMed 35244208Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19: a rapid review. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.
- Derived from this study: PubMed 35165110Erdem S, Ipek F, Bars A, Genc V, Erpek E, Mohammadi S, Altinata A, Akar S. Investigating the effect of macro-scale estimators on worldwide COVID-19 occurrence and mortality through regression analysis using online country-based data sources. BMJ Open. 2022 Feb 14;12(2):e055562. doi: 10.1136/bmjopen-2021-055562.
- Derived from this study: PubMed 34996756INSPIRATION-S Investigators. Atorvastatin versus placebo in patients with covid-19 in intensive care: randomized controlled trial. BMJ. 2022 Jan 7;376:e068407. doi: 10.1136/bmj-2021-068407.
- Derived from this study: PubMed 33734299INSPIRATION Investigators; Sadeghipour P, Talasaz AH, Rashidi F, Sharif-Kashani B, Beigmohammadi MT, Farrokhpour M, Sezavar SH, Payandemehr P, Dabbagh A, Moghadam KG, Jamalkhani S, Khalili H, Yadollahzadeh M, Riahi T, Rezaeifar P, Tahamtan O, Matin S, Abedini A, Lookzadeh S, Rahmani H, Zoghi E, Mohammadi K, Sadeghipour P, Abri H, Tabrizi S, Mousavian SM, Shahmirzaei S, Bakhshandeh H, Amin A, Rafiee F, Baghizadeh E, Mohebbi B, Parhizgar SE, Aliannejad R, Eslami V, Kashefizadeh A, Kakavand H, Hosseini SH, Shafaghi S, Ghazi SF, Najafi A, Jimenez D, Gupta A, Madhavan MV, Sethi SS, Parikh SA, Monreal M, Hadavand N, Hajighasemi A, Maleki M, Sadeghian S, Piazza G, Kirtane AJ, Van Tassell BW, Dobesh PP, Stone GW, Lip GYH, Krumholz HM, Goldhaber SZ, Bikdeli B. Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial. JAMA. 2021 Apr 27;325(16):1620-1630. doi: 10.1001/jama.2021.4152.
- COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up: JACC State-of-the-Art ReviewLink provided by the sponsor.
- Pharmacological Agents Targeting Thromboinflammation in COVID-19: Review and Implications for Future ResearchLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Parham Sadeghipour, MD principal investigator
Rajaie Cardiovascular Medical and Research Center
Behnood Bikdeli, MD, MS principal investigator
Brigham and Women's Hospital, Harvard Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing intermediate dose Enoxaparin/ unfractionated heparin, standard prophylactic dose Enoxaparin/ unfractionated heparin and Atorvastatin 20mg in people with Covid19, run by Rajaie Cardiovascular Medical and Research Center at 1 site in Iran.
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 9 inclusion and 16 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 17 Aug 2021. 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 Iran. 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 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?
a composite of acute VTE, arterial thrombosis, treatment with ECMO, or all-cause mortality (time frame: 30 days from enrollment). 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 NCT04486508, which also lists 6 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 17 Aug 2021.