EBQ:PEITHO Trial - Revision history

SuperD: /* Conclusion */

2019-12-31T10:00:31Z

Conclusion

← Revisión anterior		Revisión del 10:00 31 dic 2019
Línea 19:		Línea 19:

	==Conclusion==		==Conclusion==
	*'''Fibrinolytic therapy prevented hemodynamic ~~compensation~~ but at the risk of increased hemorrhage and stroke'''		*'''Fibrinolytic therapy prevented hemodynamic decompensation but at the risk of increased hemorrhage and stroke'''

	==Major Points==		==Major Points==

Kghaffarian: /* Criticisms & Further Discussion */

2014-11-29T19:33:25Z

Criticisms & Further Discussion

← Revisión anterior		Revisión del 19:33 29 nov 2014
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	*Not all placebo patients developing hemodynamic collapse received subsequent thrombolysis; likewise, almost half of those who received open-label thrombolysis had no hemodynamic collapse.		*Not all placebo patients developing hemodynamic collapse received subsequent thrombolysis; likewise, almost half of those who received open-label thrombolysis had no hemodynamic collapse.
	*Meta-analysis shows that patients with pulmonary embolism, including those who were hemodynamically stable with right ventricular dysfunction, thrombolytic therapy was associated with lower rates of all-cause mortality and increased risks of major bleeding and ICH.<ref>Chatterjee S. et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA. 2014 Jun 18;311(23):2414-21. PMID 24938564</ref> Second, in a subset of 1331 patients older than 65 years, thrombolysis was associated with a higher rate of major bleeding (12.93% vs 4.10%)<ref>Beckman JA. Thrombolytic therapy for pulmonary embolism. JAMA. 2014;311(23):2385–2386. doi:10.1001/jama.2014.5993.</ref>		*Meta-analysis shows that patients with pulmonary embolism, including those who were hemodynamically stable with right ventricular dysfunction, thrombolytic therapy was associated with lower rates of all-cause mortality and increased risks of major bleeding and ICH.<ref>Chatterjee S. et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA. 2014 Jun 18;311(23):2414-21. PMID 24938564</ref> Second, in a subset of 1331 patients older than 65 years, thrombolysis was associated with a higher rate of major bleeding (12.93% vs 4.10%)<ref>Beckman JA. Thrombolytic therapy for pulmonary embolism. JAMA. 2014;311(23):2385–2386. doi:10.1001/jama.2014.5993.</ref>
			*Meta-analysis of thrombolytics in PE found NNT=59 for all-cause mortality and NNH=79 for intracranial hemorrhage. Major bleeding was not significantly increased for patients age 65 or younger Odds ratio=1.25 <ref>Chatterjee, S et al. “Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality, Major Bleeding, and Intracranial Hemorrhage: A Meta-analysis.” (2014) JAMA 311(23):2414-2421</ref>

	==External Links==		==External Links==

Kghaffarian: add group difference

2014-11-29T19:21:27Z

add group difference

← Revisión anterior		Revisión del 19:21 29 nov 2014
Línea 71:		Línea 71:
	===Tenecteplase Group===		===Tenecteplase Group===
	*Tenecteplase 30-50 mg IV once over 5-10 seconds		*Tenecteplase 30-50 mg IV once over 5-10 seconds
	*UFH also administered		*UFH also administered
			*Significant between-group difference of receiving LWMH or fondaparinux before randomization
			(p=0.02)

	===Placebo Group===		===Placebo Group===
	*Also received UFH		*Also received UFH

Kghaffarian: defined hemodynamic collapse, added antiplatelet use okay

2014-11-29T19:15:31Z

defined hemodynamic collapse, added antiplatelet use okay

← Revisión anterior		Revisión del 19:15 29 nov 2014
Línea 50:		Línea 50:
	*Right ventricular dysfunction confirmed by echocardiography or spiral computed tomography of the chest and a positive troponin I or T test<ref>http://clinicaltrials.gov/show/NCT00639743</ref>		*Right ventricular dysfunction confirmed by echocardiography or spiral computed tomography of the chest and a positive troponin I or T test<ref>http://clinicaltrials.gov/show/NCT00639743</ref>
	===Exclusion Criteria===		===Exclusion Criteria===
	*Haemodynamic collapse at presentation as defined ~~above~~		*Haemodynamic collapse at presentation as defined below:<br />
	*Known significant bleeding risk		**need for CPR
			**SBP<90 for 15min
			**SBP drop 40mmHg x 15min plus end organ hypoperfusion (cold ext, low UOP, AMS)
			**need for pressors
			*Known significant bleeding risk (anti-platelet use not an exclusion)
	*Administration of thrombolytic agents within the previous 4 days		*Administration of thrombolytic agents within the previous 4 days
	*Vena cava filter insertion or pulmonary thrombectomy within the previous 4 days		*Vena cava filter insertion or pulmonary thrombectomy within the previous 4 days
Línea 61:		Línea 65:
	*Known coagulation disorder (including vitamin K antagonists)		*Known coagulation disorder (including vitamin K antagonists)
	*Any other condition that the investigator feels would place the patient at increased risk if the investigational therapy is initiated		*Any other condition that the investigator feels would place the patient at increased risk if the investigational therapy is initiated

	==Interventions==		==Interventions==
	*Both groups were initiated on unfractionated heparin (UFH) immediately after randomization with goal ptt 2.0-2.5x the upper limit of normal		*Both groups were initiated on unfractionated heparin (UFH) immediately after randomization with goal ptt 2.0-2.5x the upper limit of normal

Kghaffarian: fixed spacing

2014-11-29T19:09:06Z

fixed spacing

← Revisión anterior		Revisión del 19:09 29 nov 2014
Línea 22:		Línea 22:

	==Major Points==		==Major Points==
	The Pulmonary Embolism Thrombolysis (PEITHO) trial evaluated a single-dose tenecteplase with heparin therapy for the treatment of “intermediate risk” acute pulmonary embolism. Intermediate risk was defined as patient with pulmonary embolism in addition to right ventricular dysfunction on imaging, and elevated cardiac biomarkers. For the primary ''composite''endpoint of death or hemodynamic deterioration within 7 days, 2.6% of patients in the immediate thrombolysis group met the outcome vs. 5.6% of patients in the usual treatment arm (OR 0.44, p=0.02).		The Pulmonary Embolism Thrombolysis (PEITHO) trial evaluated a single-dose tenecteplase with heparin therapy for the treatment of “intermediate risk” acute pulmonary embolism. Intermediate risk was defined as patient with pulmonary embolism in addition to right ventricular dysfunction on imaging, and elevated cardiac biomarkers. For the primary ''composite'' endpoint of death or hemodynamic deterioration within 7 days, 2.6% of patients in the immediate thrombolysis group met the outcome vs. 5.6% of patients in the usual treatment arm (OR 0.44, p=0.02).

	Intermediate risk PE has often been used synonymously with [[Pulmonary_Embolism_(PE)#Submassive\|submassive PE]] however a standard definition has not been universally accepted. The American Heart Association has maintained that for massive pulmonary embolism, thrombolysis with tPA is an effective treatment strategy.<ref>Jaff M. et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011 Apr 26;123(16):1788-830</ref>. This trial addressed thrombolysis in patients who are hemodynamically stable but had moderate PE evidenced on CTA. Commonly, the group termed, sub-massive PE includes patients with elevated troponin, BNP, or RV dysfunction on echocardiogram.. The standard of treatment for the [[Pulmonary_Embolism_(PE)#Submassive\|sub-massive PE]] group has been unclear and thrombolysis has not been standard care for treatment, with most of these patients receiving heparin to decrease clot propagation while clot is slowly broken down<ref>Konstantinides S. Association between thrombolytic treatment and the prognosis of hemodynamically stable patients with major pulmonary embolism: results of a multicenter registry. Circulation 1997;96: 882e888</ref>		Intermediate risk PE has often been used synonymously with [[Pulmonary_Embolism_(PE)#Submassive\|submassive PE]] however a standard definition has not been universally accepted. The American Heart Association has maintained that for massive pulmonary embolism, thrombolysis with tPA is an effective treatment strategy.<ref>Jaff M. et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011 Apr 26;123(16):1788-830</ref>. This trial addressed thrombolysis in patients who are hemodynamically stable but had moderate PE evidenced on CTA. Commonly, the group termed, sub-massive PE includes patients with elevated troponin, BNP, or RV dysfunction on echocardiogram.. The standard of treatment for the [[Pulmonary_Embolism_(PE)#Submassive\|sub-massive PE]] group has been unclear and thrombolysis has not been standard care for treatment, with most of these patients receiving heparin to decrease clot propagation while clot is slowly broken down<ref>Konstantinides S. Association between thrombolytic treatment and the prognosis of hemodynamically stable patients with major pulmonary embolism: results of a multicenter registry. Circulation 1997;96: 882e888</ref>

Kghaffarian: emphasized primary outcome was a composite endpoint

2014-11-29T19:05:45Z

emphasized primary outcome was a composite endpoint

← Revisión anterior		Revisión del 19:05 29 nov 2014
Línea 22:		Línea 22:

	==Major Points==		==Major Points==
	The Pulmonary Embolism Thrombolysis (PEITHO) trial evaluated a single-dose tenecteplase with heparin therapy for the treatment of “intermediate risk” acute pulmonary embolism. Intermediate risk was defined as patient with pulmonary embolism in addition to right ventricular dysfunction on imaging, and elevated cardiac biomarkers. For the primary endpoint of death or hemodynamic deterioration within 7 days, 2.6% of patients in the immediate thrombolysis group met the outcome vs. 5.6% of patients in the usual treatment arm (OR 0.44, p=0.02).		The Pulmonary Embolism Thrombolysis (PEITHO) trial evaluated a single-dose tenecteplase with heparin therapy for the treatment of “intermediate risk” acute pulmonary embolism. Intermediate risk was defined as patient with pulmonary embolism in addition to right ventricular dysfunction on imaging, and elevated cardiac biomarkers. For the primary ''composite''endpoint of death or hemodynamic deterioration within 7 days, 2.6% of patients in the immediate thrombolysis group met the outcome vs. 5.6% of patients in the usual treatment arm (OR 0.44, p=0.02).

	Intermediate risk PE has often been used synonymously with [[Pulmonary_Embolism_(PE)#Submassive\|submassive PE]] however a standard definition has not been universally accepted. The American Heart Association has maintained that for massive pulmonary embolism, thrombolysis with tPA is an effective treatment strategy.<ref>Jaff M. et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011 Apr 26;123(16):1788-830</ref>. This trial addressed thrombolysis in patients who are hemodynamically stable but had moderate PE evidenced on CTA. Commonly, the group termed, sub-massive PE includes patients with elevated troponin, BNP, or RV dysfunction on echocardiogram.. The standard of treatment for the [[Pulmonary_Embolism_(PE)#Submassive\|sub-massive PE]] group has been unclear and thrombolysis has not been standard care for treatment, with most of these patients receiving heparin to decrease clot propagation while clot is slowly broken down<ref>Konstantinides S. Association between thrombolytic treatment and the prognosis of hemodynamically stable patients with major pulmonary embolism: results of a multicenter registry. Circulation 1997;96: 882e888</ref>		Intermediate risk PE has often been used synonymously with [[Pulmonary_Embolism_(PE)#Submassive\|submassive PE]] however a standard definition has not been universally accepted. The American Heart Association has maintained that for massive pulmonary embolism, thrombolysis with tPA is an effective treatment strategy.<ref>Jaff M. et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011 Apr 26;123(16):1788-830</ref>. This trial addressed thrombolysis in patients who are hemodynamically stable but had moderate PE evidenced on CTA. Commonly, the group termed, sub-massive PE includes patients with elevated troponin, BNP, or RV dysfunction on echocardiogram.. The standard of treatment for the [[Pulmonary_Embolism_(PE)#Submassive\|sub-massive PE]] group has been unclear and thrombolysis has not been standard care for treatment, with most of these patients receiving heparin to decrease clot propagation while clot is slowly broken down<ref>Konstantinides S. Association between thrombolytic treatment and the prognosis of hemodynamically stable patients with major pulmonary embolism: results of a multicenter registry. Circulation 1997;96: 882e888</ref>

Ostermayer at 14:42, 15 September 2014

2014-09-15T14:42:18Z

← Revisión anterior		Revisión del 14:42 15 sep 2014
Línea 13:		Línea 13:
	\| fulltexturl= http://www.nejm.org/doi/full/10.1056/NEJMoa1302097		\| fulltexturl= http://www.nejm.org/doi/full/10.1056/NEJMoa1302097
	\| pdfurl=http://theddx.org/papers/PEITHO.pdf		\| pdfurl=http://theddx.org/papers/PEITHO.pdf
	\| status="Complete"		\| status=Complete
	}}		}}
	==Clinical Question==		==Clinical Question==

Ostermayer: /* Interventions */

2014-09-15T14:40:18Z

Interventions

← Revisión anterior		Revisión del 14:40 15 sep 2014
Línea 62:		Línea 62:
	*Any other condition that the investigator feels would place the patient at increased risk if the investigational therapy is initiated		*Any other condition that the investigator feels would place the patient at increased risk if the investigational therapy is initiated
	==Interventions==		==Interventions==
	*Both groups were initiated on unfractionated heparin (UFH) immediately after randomization with goal ptt 2.0-2.5x the upper limit of normal ~~(factor Xa levels 0.3-0.7 units/mL)~~		*Both groups were initiated on unfractionated heparin (UFH) immediately after randomization with goal ptt 2.0-2.5x the upper limit of normal
	*No other anticoagulant was allowed until 48 hours after randomization		*No other anticoagulant was allowed until 48 hours after randomization
	===Tenecteplase Group===		===Tenecteplase Group===
	*Tenecteplase 30-50 mg IV once over 5-10 seconds ~~(dose varied by weight<ref>[http://www.nejm.org/doi/suppl/10.1056/NEJMoa1302097/suppl_file/nejmoa1302097_appendix.pdf#page=10 Supplementary appendix, table S1.]</ref>)~~		*Tenecteplase 30-50 mg IV once over 5-10 seconds
	*UFH also administered		*UFH also administered
	===Placebo Group===		===Placebo Group===

Ostermayer: /* Criticisms & Further Discussion */

2014-09-15T14:39:28Z

Criticisms & Further Discussion

← Revisión anterior		Revisión del 14:39 15 sep 2014
Línea 101:		Línea 101:
	*Half of the deaths in the placebo arm were "sudden unexplained" or "other" compared with bleeding or stroke complications in the thrombolysis arm		*Half of the deaths in the placebo arm were "sudden unexplained" or "other" compared with bleeding or stroke complications in the thrombolysis arm
	*Not all placebo patients developing hemodynamic collapse received subsequent thrombolysis; likewise, almost half of those who received open-label thrombolysis had no hemodynamic collapse.		*Not all placebo patients developing hemodynamic collapse received subsequent thrombolysis; likewise, almost half of those who received open-label thrombolysis had no hemodynamic collapse.
	*Meta-analysis shows that patients with pulmonary embolism, including those who were hemodynamically stable with right ventricular dysfunction, thrombolytic therapy was associated with lower rates of all-cause mortality and increased risks of major bleeding and ICH.<ref>Chatterjee S. et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA. 2014 Jun 18;311(23):2414-21. PMID 24938564</ref> Second, in a subset of 1331 ~~pa tients~~ older than 65 years, thrombolysis was associated with a higher rate of major bleeding (12.93% vs 4.10%)<ref>Beckman JA. Thrombolytic therapy for pulmonary embolism. JAMA. 2014;311(23):2385–2386. doi:10.1001/jama.2014.5993.</ref>		*Meta-analysis shows that patients with pulmonary embolism, including those who were hemodynamically stable with right ventricular dysfunction, thrombolytic therapy was associated with lower rates of all-cause mortality and increased risks of major bleeding and ICH.<ref>Chatterjee S. et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA. 2014 Jun 18;311(23):2414-21. PMID 24938564</ref> Second, in a subset of 1331 patients older than 65 years, thrombolysis was associated with a higher rate of major bleeding (12.93% vs 4.10%)<ref>Beckman JA. Thrombolytic therapy for pulmonary embolism. JAMA. 2014;311(23):2385–2386. doi:10.1001/jama.2014.5993.</ref>

	==External Links==		==External Links==

Ostermayer at 21:22, 7 September 2014

2014-09-07T21:22:27Z

← Revisión anterior		Revisión del 21:22 7 sep 2014
Línea 13:		Línea 13:
	\| fulltexturl= http://www.nejm.org/doi/full/10.1056/NEJMoa1302097		\| fulltexturl= http://www.nejm.org/doi/full/10.1056/NEJMoa1302097
	\| pdfurl=http://theddx.org/papers/PEITHO.pdf		\| pdfurl=http://theddx.org/papers/PEITHO.pdf
			\| status="Complete"
	}}		}}
	==Clinical Question==		==Clinical Question==