Trials

Question 1

Sotatercept approval trial

Answer 1

NEJM 2023- STELLAR trial

Patients- group I PAH, WHO FC II or III on stable background therapy

Outcome-
(1) 6MWT at 24 weeks
(2) PVR, NT-pro-BNP

Question 2

2 drugs aside from riociguat to have benefit in CTEPH patients (and name of trials)

Answer 2

Non-operable CTEPH:

-macitentan: MERIT-1, Lancet 2017
-subQ treprostinil: CTrePH, Lancet 2019

Question 3

Name of riociguat trial

Answer 3

Riociguat trial: Chest-1, 2013 NEJM

Phase 3 RCT, 261 pts with inoperable or persistent/recurrent CTEPH to placebo vs. riociguat

Primary outcome- 6MWT
Secondary outcomes- PVR, WHO FC, pro-BNP
^^all 4 significantly better in riociguat group

Question 4

Key trial describing features of portopulmonary HTN

(a) Big hemodynamic difference from primary PAH

Answer 4

Chest 1997 (Kuo et al)- compared 30 patients with portopulmonary (PPAH) with 30 primary PAH w/o liver disease and 30 liver disease w/o PH

(a) PPAH have higher cardiac index and lower SVR than primary PAH = systemic hemodynamic profile more similar to chronic liver disease

Question 5

Portopulmonary HTN

(a) Big hemodynamic difference from primary PAH
(b) Big respiratory (acid/base) difference from chronic liver disease

Answer 5

Portopulmonary HTN = loosely defined as association of primary PH with portal hypertension

(a) Portopulmonary has higher cardiac output/index and lower SVR than primary PH (reflecting hyperdynamic circulation of chronic liver disease)

(b) Portopulmonary has accentuated respiratory alkalosis (lower pCO2), possible that a pCO2 cutoff > 30 could be helpful screening tool for live transplant candidates to rule out severe portopulmonary HTN

Question 6

Sotatercept 3/2025 NEJM ZENITH trial- patients, outcome

Answer 6

ZENITH trial- Sotatercept (activin signaling inhibitor) reduced admissions for worsening PAH in patient’s with high risk of one year mortality from PAH (REVEAL >= 9)

Patients- 172 pts with WHO FC III or IV on background double or quadruple PAH therapy

Outcome- composite of death from any cause, lung transplant, or admission for PAH (which was the most common endpoint)

Question 7

In ZENITH trial (sotatercept 3/2025, PAH pts with high risk of 1 year mortality), what was the average change in

(a) mPAP
(b) PVR
(c) 6MWT

Answer 7

(a) ~15mmHg reduction in mPAP
(b) 2.5 WU reduction in PVR
(c) 45m improvement in 6MWT