Pericardial EffusionPhase 3IMPI-2NCT02673879
IMPI 2 - A Trial of Intrapericardial Alteplase in Large Pericardial Effusion
A Phase 3 study testing Pericardiocentesis with Alteplase and Conventional Pericardiocentesis in people with Pericardial Effusion, run by University of Cape Town at 1 site in South Africa.
Trial summary
The Second Investigation of the Management of Pericarditis (IMPI-2) Trial will compare the effectiveness and safety of complete percutaneous pericardial drainage facilitated by intrapericardial alteplase (recombinant human tissue-type plasminogen activator) to conventional pericardiocentesis when indicated in 2176… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pericardial Effusion
- What is being tested?
- Pericardiocentesis with Alteplase and Conventional Pericardiocentesis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,176 participants
- Where
- 1 siteSouth Africa
- Study dates
- Feb 2016to Jan 2020
- 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
- Age ≥ 18 years of age;
- Confirmed large pericardial effusion on echocardiography (i.e., echo free space ≥1 cm anterior to the right ventricle of the heart in diastole);
- Willingness to participate for the full duration of the trial (i.e., 12 months); and
- Provision of written informed consent.
Who cannot join
- Age < 18 years;
- Uraemic pericarditis (i.e., urea > 21.4 mmol/l);
- Thrombocytopenia (i.e., < 100,000 platelets per µl);
- Presence of a contra-indication to the administration of a fibrinolytic agent (i.e., major haemorrhage or major trauma; coincidental stroke; major surgery in the previous 5 days; blood pressure >200/100 mmHg).
Trial locations and contacts
1 site in 1 country.
South Africa1 site, 1 recruiting
- Recruiting
Groote Schuur Hospital
Cape Town, Western Cape, 7925
Shaheen Pandie, MMed (Med), +27823199030, s.pandie@uct.ac.za
Veronica Francis, +27832449895, veronica.francis@uct.ac.za
About this study
Official title: A Trial of Complete Percutaneous Pericardial Drainage Facilitated by Intrapericardial Alteplase Compared to Conventional Pericardiocentesis When Indicated in Adults With Large Pericardial Effusion Due to Tuberculous and Non-tuberculous Pericarditis
The Second Investigation of the Management of Pericarditis (IMPI-2) Trial will compare the effectiveness and safety of complete percutaneous pericardial drainage facilitated by intrapericardial alteplase (recombinant human tissue-type plasminogen activator) to conventional pericardiocentesis when indicated in 2176 patients with large pericardial effusion due to tuberculous and non-tuberculous pericarditis. An internal pilot study of 218 patients will initially confirm the feasibility of conducting a large-scale multi-centre clinical trial of intrapericardial fibrinolysis in patients with large pericardial effusion, and also provide preliminary safety data, following a dose finding study of intrapericardial alteplase.
Read the detailed description
Intrapericardial fibrinolytic agents are used in the drainage of tuberculous, purulent, neoplastic and other inflammatory pericardial effusions to prevent recurrent effusions and constrictive pericarditis. This use is based on evidence from case reports and a small trial that did not have the statistical power to reliably evaluate the effect of pericardial drainage facilitated by intrapericardial fibrinolysis on safety and important clinical outcomes.
The Second Investigation of the Management of Pericarditis (IMPI-2) Trial will compare the effectiveness and safety of complete percutaneous pericardial drainage facilitated by intrapericardial alteplase (recombinant human tissue-type plasminogen activator) to conventional pericardiocentesis when indicated in 2176 patients with large pericardial effusion due to tuberculous and non-tuberculous pericarditis. An internal pilot study of 218 patients will initially confirm the feasibility of conducting a large-scale multi-centre clinical trial of intrapericardial fibrinolysis in patients with large pericardial effusion, and also provide preliminary safety data, following a dose finding study of intrapericardial alteplase.
Hypothesis: We hypothesise that patients with large pericardial effusion randomized to intrapericardial alteplase to ensure complete pericardial drainage will have at least a 35% reduction in cardiac tamponade requiring pericardiocentesis or constrictive pericarditis compared to conventional pericardiocentesis when indicated.
Objectives: The primary objectives of the IMPI-2 Trial are:
- To demonstrate the feasibility of conducting a multicentre clinical trial of intrapericardial fibrinolysis in patients with large pericardial effusion, and to assess the safety of intrapericardial alteplase in an internal pilot study, and
- To determine the effectiveness of intrapericardial alteplase in reducing the composite outcome of cardiac tamponade requiring pericardiocentesis or constrictive pericarditis in patients with large pericardial effusion in the full trial.
Should the internal pilot study demonstrate feasibility and safety; all 218 patients will be rolled-over into the full scale IMPI-2 trial of 2176 participants. The primary outcome is the first occurrence of cardiac tamponade requiring pericardiocentesis or constrictive pericarditis. The secondary safety endpoint is safety of intrapericardial fibrinolysis measured by effect on major bleeding, and serious and non-serious adverse events. The secondary efficacy outcomes are constrictive pericarditis, and cardiac tamponade requiring pericardiocentesis, analysed separately, and persistent or recurrent pericardial effusion without cardiac tamponade, hospitalisation, and death. The secondary diagnostic outcomes are proportion with bacteriologically confirmed tuberculosis from any organ or tissue; time to diagnosis of bacteriologically confirmed tuberculosis in days; accuracy of novel tests for the diagnosis of tuberculosis; proportion with specific diagnosis of any pericardial disease; time to diagnosis of a specific pericardial disease in days.
Study Design: IMPI-2 is a prospective randomized open blinded end-point trial that will enroll 2176 patients with large pericardial effusion over 36 months from up to 30 centres in South Africa and Africa. Eligible patients will be randomly assigned to receive complete pericardial drainage facilitated by intrapericardial fibrinolysis or conventional pericardiocentesis when indicated on enrollment to the study. Patients will be followed at 2 weeks, 6 weeks, 12 weeks, and in months 6, and 12 after enrollment. The IMPI Project Office, University of Cape Town, South Africa will manage and coordinate the study in association with the Pericarditis Research Unit, Walter Sisulu University, South Africa and the Population Health Research Institute, McMaster University, Canada.
Importance: IMPI-2 addresses very serious complications of large pericardial effusion (i.e., cardiac tamponade and constrictive pericarditis), which are associated with high mortality despite pericardiocentesis or pericardiectomy. This study will utilise the research network that was established by the IMPI trial which was completed in 2014.
- Conditions
- Pericardial Effusion
- Being tested
- Pericardiocentesis with Alteplase, Conventional Pericardiocentesis
- Medical subject headings
- Pericardial Effusion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pericardiocentesis with AlteplaseOther
Complete percutaneous pericardial drainage facilitated by intrapericardial alteplase
Conventional PericardiocentesisOther
Conventional pericardiocentesis when indicated
| Study group | Role | What they receive |
|---|---|---|
| Pericardiocentesis with Alteplase | Active comparator | Complete percutaneous pericardial drainage facilitated by intrapericardial alteplase. Receives: Other: Pericardiocentesis with Alteplase |
| Conventional Pericardiocentesis | Other | Conventional pericardiocentesis when indicated. Receives: Other: Conventional Pericardiocentesis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite outcome of cardiac tamponade requiring pericardiocentesis or constrictive pericarditis.
Cardiac tamponade requiring pericardiocentesis shall refer to a combination of physical and echocardiographic findings, i.e., patients with clinical signs of tachycardia (> 90 bpm), hypotension (systolic blood pressure < 100 mmHg), elevated jugular venous pressure and/or pulsus paradoxus > 10 mmHg plus evidence of a large pericardial effusion with echocardiographic signs of tamponade in the absence of other cardiac disease, as defined in the IMPI trial.
Constrictive pericarditis shall refer to a combination of physical and echocardiographic findings (i.e., patients with a prior history of pericardial effusion who have pulsus paradoxus, a raised jugular venous pressure with or without evidence of pericardial thickening on imaging) in the absence of either large pericardial effusion or other cardiac disease, as described in the IMPI trial.
Measured: 12 months
Secondary outcomes (10)
Major bleeding
Defined as clinically overt bleeding accompanied by one or more of the following: a decrease in the haemoglobin level of 2 g per decilitre or more over a 24-hour period, transfusion of 2 or more units of packed red cells, bleeding at a critical site (intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, or retroperitoneal), or fatal bleeding
Measured: 12 months
Clinically relevant non-major bleeding
Defined as clinically overt bleeding that does not satisfy the criteria for major bleeding and that leads to hospital admission, physician-guided medical or surgical treatment.
Measured: 12 months
Any bleeding
Any other form of bleeding that is not covered by safety outcomes 1-3
Measured: 12 months
Other adverse events
Any other adverse events
Measured: 12 months
Persistent pericardial effusion without cardiac tamponade
Refers to the echocardiographic presence of a pericardial effusion without criteria for cardiac tamponade requiring pericarditis during follow-up visits. The pericardial effusion is the same size or larger than that measured at the time of enrollment (where no pericardiocentesis was done) or post-pericardiocentesis.
Measured: 12 months
Recurrent pericardial effusion without cardiac tamponade
Refers to the echocardiographic presence of a pericardial effusion without criteria for cardiac tamponade requiring pericarditis during follow-up visits. Recurrence is present in the context of re-appearance of a pericardial effusion in the context where complete drainage was performed.
Measured: 12 months
Hospitalisation for any cause; and death from any cause
Refers to admission to hospital for at least 24 hours for any reason.
Measured: 12 months
Cardiac tamponade requiring pericardiocentesis
Cardiac tamponade requiring pericardiocentesis shall refer to a combination of physical and echocardiographic findings, i.e., patients with clinical signs of tachycardia (> 90 bpm), hypotension (systolic blood pressure < 100 mmHg), elevated jugular venous pressure and/or pulsus paradoxus > 10 mmHg plus evidence of a large pericardial effusion with echocardiographic signs of tamponade in the absence of other cardiac disease, as defined in the IMPI trial.
Measured: 12 months
Constrictive pericarditis
Constrictive pericarditis shall refer to a combination of physical and echocardiographic findings (i.e., patients with a prior history of pericardial effusion who have pulsus paradoxus, a raised jugular venous pressure with or without evidence of pericardial thickening on imaging) in the absence of either large pericardial effusion or other cardiac disease, as described in the IMPI trial.
Measured: 12 months
Death
Death from any cause
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2016 (estimated)
- Study startFeb 2016
- Primary completionJul 2019 (estimated)
- Study completionJan 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pericardial EffusionStudies 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
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 2,176 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Cape Town
- Sponsor type
- University, hospital or other
- Collaborators
- Walter Sisulu University, Population Health Research Institute
- Responsible party
- Principal investigator, Bongani M Mayosi, University of Cape Town
- Investigators
- Bongani M Mayosi, DPhil, Principal investigator, University of Cape Town
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02673879
- Sponsor's protocol ID
- HREC REF No. 370/2015
- Acronym
- IMPI-2
- Status last verified
- Feb 2016
- First submitted
- 1 Feb 2016
- Last updated
- 2 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Individual patient data will be made available on request at the end of the study, subject to approval by the Steering Committee of the IMPI-2 Trial.
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Trial of Complete Percutaneous Pericardial Drainage Facilitated by Intrapericardial Alteplase Compared to Conventional Pericardiocentesis When Indicated in Adults With Large Pericardial Effusion Due to Tuberculous and Non-tuberculous Pericarditis
- ClinicalTrials.gov ID
- NCT02673879
- Acronym / sponsor ID
- IMPI-2 / HREC REF No. 370/2015
- Conditions
- Pericardial Effusion
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 2,176 participants (estimated)
- Lead sponsor
- University of Cape TownUniversity, hospital or other
- Collaborators
- Walter Sisulu University, Population Health Research Institute
- Study start
- Feb 2016
- Primary completion
- Jul 2019 (estimated)
- Study completion
- Jan 2020 (estimated)
- First posted
- 4 Feb 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.
The Second Investigation of the Management of Pericarditis (IMPI-2) Trial will compare the effectiveness and safety of complete percutaneous pericardial drainage facilitated by intrapericardial alteplase (recombinant human tissue-type plasminogen activator) to conventional pericardiocentesis when indicated in 2176 patients with large pericardial effusion due to tuberculous and non-tuberculous pericarditis. An internal pilot study of 218 patients will initially confirm the feasibility of conducting a large-scale multi-centre clinical trial of intrapericardial fibrinolysis in patients with large pericardial effusion, and also provide preliminary safety data, following a dose finding study of intrapericardial alteplase.
Detailed description
Intrapericardial fibrinolytic agents are used in the drainage of tuberculous, purulent, neoplastic and other inflammatory pericardial effusions to prevent recurrent effusions and constrictive pericarditis. This use is based on evidence from case reports and a small trial that did not have the statistical power to reliably evaluate the effect of pericardial drainage facilitated by intrapericardial fibrinolysis on safety and important clinical outcomes.
The Second Investigation of the Management of Pericarditis (IMPI-2) Trial will compare the effectiveness and safety of complete percutaneous pericardial drainage facilitated by intrapericardial alteplase (recombinant human tissue-type plasminogen activator) to conventional pericardiocentesis when indicated in 2176 patients with large pericardial effusion due to tuberculous and non-tuberculous pericarditis. An internal pilot study of 218 patients will initially confirm the feasibility of conducting a large-scale multi-centre clinical trial of intrapericardial fibrinolysis in patients with large pericardial effusion, and also provide preliminary safety data, following a dose finding study of intrapericardial alteplase.
Hypothesis: We hypothesise that patients with large pericardial effusion randomized to intrapericardial alteplase to ensure complete pericardial drainage will have at least a 35% reduction in cardiac tamponade requiring pericardiocentesis or constrictive pericarditis compared to conventional pericardiocentesis when indicated.
Objectives: The primary objectives of the IMPI-2 Trial are:
- To demonstrate the feasibility of conducting a multicentre clinical trial of intrapericardial fibrinolysis in patients with large pericardial effusion, and to assess the safety of intrapericardial alteplase in an internal pilot study, and
- To determine the effectiveness of intrapericardial alteplase in reducing the composite outcome of cardiac tamponade requiring pericardiocentesis or constrictive pericarditis in patients with large pericardial effusion in the full trial.
Should the internal pilot study demonstrate feasibility and safety; all 218 patients will be rolled-over into the full scale IMPI-2 trial of 2176 participants. The primary outcome is the first occurrence of cardiac tamponade requiring pericardiocentesis or constrictive pericarditis. The secondary safety endpoint is safety of intrapericardial fibrinolysis measured by effect on major bleeding, and serious and non-serious adverse events. The secondary efficacy outcomes are constrictive pericarditis, and cardiac tamponade requiring pericardiocentesis, analysed separately, and persistent or recurrent pericardial effusion without cardiac tamponade, hospitalisation, and death. The secondary diagnostic outcomes are proportion with bacteriologically confirmed tuberculosis from any organ or tissue; time to diagnosis of bacteriologically confirmed tuberculosis in days; accuracy of novel tests for the diagnosis of tuberculosis; proportion with specific diagnosis of any pericardial disease; time to diagnosis of a specific pericardial disease in days.
Study Design: IMPI-2 is a prospective randomized open blinded end-point trial that will enroll 2176 patients with large pericardial effusion over 36 months from up to 30 centres in South Africa and Africa. Eligible patients will be randomly assigned to receive complete pericardial drainage facilitated by intrapericardial fibrinolysis or conventional pericardiocentesis when indicated on enrollment to the study. Patients will be followed at 2 weeks, 6 weeks, 12 weeks, and in months 6, and 12 after enrollment. The IMPI Project Office, University of Cape Town, South Africa will manage and coordinate the study in association with the Pericarditis Research Unit, Walter Sisulu University, South Africa and the Population Health Research Institute, McMaster University, Canada.
Importance: IMPI-2 addresses very serious complications of large pericardial effusion (i.e., cardiac tamponade and constrictive pericarditis), which are associated with high mortality despite pericardiocentesis or pericardiectomy. This study will utilise the research network that was established by the IMPI trial which was completed in 2014.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pericardiocentesis with Alteplase | Active comparator | Other: Pericardiocentesis with AlteplaseComplete percutaneous pericardial drainage facilitated by intrapericardial alteplase. |
| Conventional Pericardiocentesis | Other | Other: Conventional PericardiocentesisConventional pericardiocentesis when indicated. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age ≥ 18 years of age;
- Confirmed large pericardial effusion on echocardiography (i.e., echo free space ≥1 cm anterior to the right ventricle of the heart in diastole);
- Willingness to participate for the full duration of the trial (i.e., 12 months); and
- Provision of written informed consent.
Key exclusion criteria (4 listed)
- Age < 18 years;
- Uraemic pericarditis (i.e., urea > 21.4 mmol/l);
- Thrombocytopenia (i.e., < 100,000 platelets per µl);
- Presence of a contra-indication to the administration of a fibrinolytic agent (i.e., major haemorrhage or major trauma; coincidental stroke; major surgery in the previous 5 days; blood pressure >200/100 mmHg).
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 |
|---|---|---|
| Pericardiocentesis with AlteplaseComplete percutaneous pericardial drainage facilitated by intrapericardial alteplase | Other | Pericardiocentesis with Alteplase |
| Conventional PericardiocentesisConventional pericardiocentesis when indicated | Other | Conventional Pericardiocentesis |
Primary outcome
Composite outcome of cardiac tamponade requiring pericardiocentesis or constrictive pericarditis.
Time frame: 12 months
Cardiac tamponade requiring pericardiocentesis shall refer to a combination of physical and echocardiographic findings, i.e., patients with clinical signs of tachycardia (> 90 bpm), hypotension (systolic blood pressure < 100 mmHg), elevated jugular venous pressure and/or pulsus paradoxus > 10 mmHg plus evidence of a large pericardial effusion with echocardiographic signs of tamponade in the absence of other cardiac disease, as defined in the IMPI trial. Constrictive pericarditis shall refer to a combination of physical and echocardiographic findings (i.e., patients with a prior history of pericardial effusion who have pulsus paradoxus, a raised jugular venous pressure with or without evidence of pericardial thickening on imaging) in the absence of either large pericardial effusion or other cardiac disease, as described in the IMPI trial.
10 secondary outcomes
Major bleeding
Time frame: 12 months
Clinically relevant non-major bleeding
Time frame: 12 months
Any bleeding
Time frame: 12 months
Other adverse events
Time frame: 12 months
Persistent pericardial effusion without cardiac tamponade
Time frame: 12 months
Recurrent pericardial effusion without cardiac tamponade
Time frame: 12 months
Hospitalisation for any cause; and death from any cause
Time frame: 12 months
Cardiac tamponade requiring pericardiocentesis
Time frame: 12 months
Constrictive pericarditis
Time frame: 12 months
Death
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2018.
- Individual participant dataSharing planned: Yes. Individual patient data will be made available on request at the end of the study, subject to approval by the Steering Committee of the IMPI-2 Trial.
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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.
Bongani M Mayosi, DPhil principal investigator
University of Cape Town
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 Pericardiocentesis with Alteplase and Conventional Pericardiocentesis in people with Pericardial Effusion, run by University of Cape Town at 1 site in South Africa.
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 4 inclusion and 4 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 2 May 2018. 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 South Africa. 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 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Veronica Francis (+27832449895, veronica.francis@uct.ac.za), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite outcome of cardiac tamponade requiring pericardiocentesis or constrictive pericarditis. (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 May 2018.