Pulmonary Embolism With Right Ventricle EnlargementPhase 3DiPERNCT02268903
Diuretic Versus Placebo in Pulmonary Embolism
A Phase 3 study testing Diuretics : Furosemide in people with Pulmonary Embolism With Right Ventricle Enlargement, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Pulmonary Embolism (PE) is a frequent and severe disease with an annual incidence of about 75000 cases in France and a short-term mortality rate of about 10%. Death is usually related to an acute right ventricular (RV) failure due to the increase in right ventricular afterload. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Embolism With Right Ventricle Enlargement
- What is being tested?
- Diuretics : Furosemide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 270 participants
- Where
- 1 siteFrance
- Study dates
- 13 Apr 2015to May 2018
- 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
- Patients aged 18 years and over with
- Symptomatic acute pulmonary embolism with first clinical symptoms within 15 days, and objectively confirmed by CT scan
- RV dysfunction (≥1 criterion) confirmed by elevated BNP value or echocardiography or spiral computed tomography of the chest:
- Echocardiography
- o Right/Left ventricular end diastolic diameter > 1(apical or subcostal 4-chamber view)
- Computed tomography
Show all 12Show fewer
- o Right/Left short-axis diameter ratio>0.9 (transverse plane)
- Positive Nt-proBNP (>600) or BNP>200 pg/mL
- One abnormal following PESI criteria
- Heart Rate>110/min
- Systolic blood pressure<100mmHg
- Arterial oxyhemoglobin level<90% on room air or after 5 minutes of oxygen withdrawal.
Who cannot join
- Cardiogenic shock requiring thrombolysis
- Previous significant left ventricular insufficiency (LVEF<45%)
- Systolic blood pressure<90mmHg at admission
- Age ≤ 18 years
- Pregnancy
- No health insurance
Show all 16Show fewer
- Patients deprived of liberty or under legal protection
- Creatinin clearance <30mL/min/m²
- hypersensibility to furosemide or its excipients
- functional renal insufficiency
- Hepatic encephalopathy
- Urinary tracks obstruction
- Hypovolemia or dehydration.
- Sever hypokalemia (K+ < 3mmol/L)
- Severe hyponatremia (Na+ < 125mmol/L)
- Ongoing hepatitis and hepatic insufficiency severe in patients with renal insufficiency or dialysis
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Henri Mondor Hospital
Créteil, 94010
Jean-Luc DUBOIS-RANDE, PU-PH, (0)1 49 81 36 02 ext. +33, jean-luc.duboisrande@hmn.aphp.fr
Dalila SELMANE, CRA, (0)1 49 81 33 86 ext. +33, dalila.selmane@hmn.aphp.fr
About this study
Official title: Diuretic Versus Placebo in Pulmonary Embolism With Right Ventricular Enlargement: a Double-blind Randomized Controlled Study
Pulmonary Embolism (PE) is a frequent and severe disease with an annual incidence of about 75000 cases in France and a short-term mortality rate of about 10%. Death is usually related to an acute right ventricular (RV) failure due to the increase in right ventricular afterload. Treatment of PE with RV failure consists in fluid expansion and thrombolysis in case of shock. However several studies suggest that fluid expansion may worsen acute RV failure by increasing RV dilatation and ischemia and left ventricular compression by RV dilatation. Thus, current guidelines regarding PE treatment remain unclear about the use of fluid expansion. In a preliminary study published by our group, we showed that diuretic treatment in the setting of PE with RV dilatation is safe and is associated with an increase in urine output, a decrease in heart rate and an increase in SpO2 in normotensive patients with oliguria. This may be related to the decrease of ventricular interdependence and enhancement of both LV and RV function.
The main objective of the study is to evaluate the 24-hours clinical benefit of furosemide in patients referred for acute PE with RV dilatation compared to placebo. The combination of urine output and sPESI clinical parameters reflects hemodynamic status. It is relevant as it indicates the disappearance of pre-shock symptoms and is therefore associated with a lower event risk. Thus, it allows early discharge of the patients from the intensive care unit.
- Being tested
- Diuretics : Furosemide, Placebo
- Keywords
- Pulmonary Embolism, Right Ventricle failure, Diuretics
- Medical subject headings
- Pulmonary Embolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Diuretics : FurosemideDrug
Furosemide 80mg in one single direct intra venous injection
PlaceboDrug
Placebo in one single direct intra venous injection
| Study group | Role | What they receive |
|---|---|---|
| Diuretics | Active comparator | Not described Receives: Drug: Diuretics : Furosemide |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary end point will be a combined clinical criterion, to reach the primary endpoint, patients have to meet all the following criteria: - Urine output> 0.5ml/kg/h - Normalization of clinical parameters of simplified PESI score
Normalization of clinical parameters of simplified PESI score :
- Heart Rate<110/min
- Systolic blood pressure≥100mmHg
- Arterial oxyhemoglobin level>90% on room air or after 5 minutes of oxygen withdrawal.
Measured: 24 hours
Secondary outcomes (4)
patients have to meet all the four following criteria: - Urine output> 0.5ml/kg/h over 24 hours - Normalization of clinical parameters of simplified PESI score - Urine output
Normalization of clinical parameters of simplified PESI score :
- Heart Rate<110/min
- Systolic blood pressure≥100mmHg
- Arterial oxyhemoglobin level>90% on room air or after 5 minutes of oxygen withdrawal.
Measured: 48 hours
- Composite criteria including death, need for catecholamine, cardiac arrest and mechanical ventilation during hospitalization and at 1 month from inclusion - NYHA score
Measured: In hospital and 1 month
o RV/LV ratio and decrease from baseline o Systolic pulmonary pressure and decrease from baseline o Tricuspid annular plane systolic expansion (TAPSE) at o Tricuspid annular plane systolic expansion (TAPSE) variation from baseline
RV/LV ratio (diameters and surfaces)
Measured: 24 hours abd 1 month
- NT-proBNP or BNP decrease at 24hours - Creatinin and liver enzymes variations at 24hours
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2014 (estimated)
- Study start13 Apr 2015
- Primary completionApr 2018 (estimated)
- Study completionMay 2018 (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 Pulmonary Embolism With Right Ventricle EnlargementStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 270 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jean-Luc DUBOIS-RANDE, PU-PH, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02268903
- Sponsor's protocol ID
- AOM 130519
- Acronym
- DiPER
- Status last verified
- Oct 2017
- First submitted
- 16 Oct 2014
- Last updated
- 19 Oct 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Wood KE. Major pulmonary embolism: review of a pathophysiologic approach to the golden hour of hemodynamically significant pulmonary embolism. Chest. 2002 Mar;121(3):877-905. doi: 10.1378/chest.121.3.877.
PubMed 11888976Lee FA. Hemodynamics of the right ventricle in normal and disease states. Cardiol Clin. 1992 Feb;10(1):59-67.
PubMed 1739960Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galie N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP; ESC Committee for Practice Guidelines (CPG). Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J. 2008 Sep;29(18):2276-315. doi: 10.1093/eurheartj/ehn310. Epub 2008 Aug 30.
PubMed 18757870Perlroth DJ, Sanders GD, Gould MK. Effectiveness and cost-effectiveness of thrombolysis in submassive pulmonary embolism. Arch Intern Med. 2007 Jan 8;167(1):74-80. doi: 10.1001/archinte.167.1.74.
PubMed 17210881Goldhaber SZ, Haire WD, Feldstein ML, Miller M, Toltzis R, Smith JL, Taveira da Silva AM, Come PC, Lee RT, Parker JA, et al. Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right-ventricular function and pulmonary perfusion. Lancet. 1993 Feb 27;341(8844):507-11. doi: 10.1016/0140-6736(93)90274-k.
PubMed 8094768Lim P, Delmas C, Sanchez O, Meneveau N, Rosario R, Bouvaist H, Bernard A, Mansourati J, Couturaud F, Sebbane M, Coste P, Rohel G, Tardy B, Biendel C, Lairez O, Ivanes F, Gallet R, Dubois-Rande JL, Fard D, Chatelier G, Simon T, Paul M, Natella PA, Layese R, Bastuji-Garin S. Diuretic vs. placebo in intermediate-risk acute pulmonary embolism: a randomized clinical trial. Eur Heart J Acute Cardiovasc Care. 2022 Jan 12;11(1):2-9. doi: 10.1093/ehjacc/zuab082.
PubMed 34632490Gallet R, Meyer G, Ternacle J, Biendel C, Brunet A, Meneveau N, Rosario R, Couturaud F, Sebbane M, Lamblin N, Bouvaist H, Coste P, Maitre B, Bastuji-Garin S, Dubois-Rande JL, Lim P. Diuretic versus placebo in normotensive acute pulmonary embolism with right ventricular enlargement and injury: a double-blind randomised placebo controlled study. Protocol of the DiPER study. BMJ Open. 2015 May 22;5(5):e007466. doi: 10.1136/bmjopen-2014-007466.
PubMed 26002690
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diuretic Versus Placebo in Pulmonary Embolism With Right Ventricular Enlargement: a Double-blind Randomized Controlled Study
- ClinicalTrials.gov ID
- NCT02268903
- Acronym / sponsor ID
- DiPER / AOM 130519
- Keywords
- Pulmonary Embolism, Right Ventricle failure, Diuretics
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 270 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 13 Apr 2015 (actual)
- Primary completion
- Apr 2018 (estimated)
- Study completion
- May 2018 (estimated)
- First posted
- 20 Oct 2014 (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.
Pulmonary Embolism (PE) is a frequent and severe disease with an annual incidence of about 75000 cases in France and a short-term mortality rate of about 10%. Death is usually related to an acute right ventricular (RV) failure due to the increase in right ventricular afterload. Treatment of PE with RV failure consists in fluid expansion and thrombolysis in case of shock. However several studies suggest that fluid expansion may worsen acute RV failure by increasing RV dilatation and ischemia and left ventricular compression by RV dilatation. Thus, current guidelines regarding PE treatment remain unclear about the use of fluid expansion. In a preliminary study published by our group, we showed that diuretic treatment in the setting of PE with RV dilatation is safe and is associated with an increase in urine output, a decrease in heart rate and an increase in SpO2 in normotensive patients with oliguria. This may be related to the decrease of ventricular interdependence and enhancement of both LV and RV function.
The main objective of the study is to evaluate the 24-hours clinical benefit of furosemide in patients referred for acute PE with RV dilatation compared to placebo. The combination of urine output and sPESI clinical parameters reflects hemodynamic status. It is relevant as it indicates the disappearance of pre-shock symptoms and is therefore associated with a lower event risk. Thus, it allows early discharge of the patients from the intensive care unit.
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 |
|---|---|---|
| Diuretics | Active comparator | Drug: Diuretics : Furosemide |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients aged 18 years and over with
- Symptomatic acute pulmonary embolism with first clinical symptoms within 15 days, and objectively confirmed by CT scan
- RV dysfunction (≥1 criterion) confirmed by elevated BNP value or echocardiography or spiral computed tomography of the chest:
- o Right/Left ventricular end diastolic diameter > 1(apical or subcostal 4-chamber view)
- o Right/Left short-axis diameter ratio>0.9 (transverse plane)
Key exclusion criteria (16 listed)
- Cardiogenic shock requiring thrombolysis
- Previous significant left ventricular insufficiency (LVEF<45%)
- Systolic blood pressure<90mmHg at admission
- Age ≤ 18 years
- Pregnancy
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 |
|---|---|---|
| Diuretics : FurosemideFurosemide 80mg in one single direct intra venous injection | Drug | Diuretics |
| PlaceboPlacebo in one single direct intra venous injection | Drug | Placebo |
Primary outcome
Primary end point will be a combined clinical criterion, to reach the primary endpoint, patients have to meet all the following criteria: - Urine output> 0.5ml/kg/h - Normalization of clinical parameters of simplified PESI score
Time frame: 24 hours
Normalization of clinical parameters of simplified PESI score : * Heart Rate<110/min * Systolic blood pressure≥100mmHg * Arterial oxyhemoglobin level>90% on room air or after 5 minutes of oxygen withdrawal.
4 secondary outcomes
patients have to meet all the four following criteria: - Urine output> 0.5ml/kg/h over 24 hours - Normalization of clinical parameters of simplified PESI score - Urine output
Time frame: 48 hours
- Composite criteria including death, need for catecholamine, cardiac arrest and mechanical ventilation during hospitalization and at 1 month from inclusion - NYHA score
Time frame: In hospital and 1 month
o RV/LV ratio and decrease from baseline o Systolic pulmonary pressure and decrease from baseline o Tricuspid annular plane systolic expansion (TAPSE) at o Tricuspid annular plane systolic expansion (TAPSE) variation from baseline
Time frame: 24 hours abd 1 month
- NT-proBNP or BNP decrease at 24hours - Creatinin and liver enzymes variations at 24hours
Time frame: 24 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2017.
- Background: PubMed 11888976Wood KE. Major pulmonary embolism: review of a pathophysiologic approach to the golden hour of hemodynamically significant pulmonary embolism. Chest. 2002 Mar;121(3):877-905. doi: 10.1378/chest.121.3.877.
- Background: PubMed 1739960Lee FA. Hemodynamics of the right ventricle in normal and disease states. Cardiol Clin. 1992 Feb;10(1):59-67.
- Background: PubMed 18757870Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galie N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP; ESC Committee for Practice Guidelines (CPG). Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J. 2008 Sep;29(18):2276-315. doi: 10.1093/eurheartj/ehn310. Epub 2008 Aug 30.
- Background: PubMed 17210881Perlroth DJ, Sanders GD, Gould MK. Effectiveness and cost-effectiveness of thrombolysis in submassive pulmonary embolism. Arch Intern Med. 2007 Jan 8;167(1):74-80. doi: 10.1001/archinte.167.1.74.
- Background: PubMed 8094768Goldhaber SZ, Haire WD, Feldstein ML, Miller M, Toltzis R, Smith JL, Taveira da Silva AM, Come PC, Lee RT, Parker JA, et al. Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right-ventricular function and pulmonary perfusion. Lancet. 1993 Feb 27;341(8844):507-11. doi: 10.1016/0140-6736(93)90274-k.
- Derived from this study: PubMed 34632490Lim P, Delmas C, Sanchez O, Meneveau N, Rosario R, Bouvaist H, Bernard A, Mansourati J, Couturaud F, Sebbane M, Coste P, Rohel G, Tardy B, Biendel C, Lairez O, Ivanes F, Gallet R, Dubois-Rande JL, Fard D, Chatelier G, Simon T, Paul M, Natella PA, Layese R, Bastuji-Garin S. Diuretic vs. placebo in intermediate-risk acute pulmonary embolism: a randomized clinical trial. Eur Heart J Acute Cardiovasc Care. 2022 Jan 12;11(1):2-9. doi: 10.1093/ehjacc/zuab082.
- Derived from this study: PubMed 26002690Gallet R, Meyer G, Ternacle J, Biendel C, Brunet A, Meneveau N, Rosario R, Couturaud F, Sebbane M, Lamblin N, Bouvaist H, Coste P, Maitre B, Bastuji-Garin S, Dubois-Rande JL, Lim P. Diuretic versus placebo in normotensive acute pulmonary embolism with right ventricular enlargement and injury: a double-blind randomised placebo controlled study. Protocol of the DiPER study. BMJ Open. 2015 May 22;5(5):e007466. doi: 10.1136/bmjopen-2014-007466.
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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.
Jean-Luc DUBOIS-RANDE, PU-PH principal investigator
Assistance Publique - Hôpitaux de Paris
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 Diuretics : Furosemide in people with Pulmonary Embolism With Right Ventricle Enlargement, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 12 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: status not confirmed, as of the sponsor's last update on 19 Oct 2017. 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 France. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jean-Luc DUBOIS-RANDE, PU-PH ((0)1 49 81 36 02 ext. +33, jean-luc.duboisrande@hmn.aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary end point will be a combined clinical criterion, to reach the primary endpoint, patients have to meet all the following criteria: - Urine output> 0.5ml/kg/h - Normalization of clinical parameters of simplified PESI score (time frame: 24 hours). 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 NCT02268903, 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 19 Oct 2017.