Ignite Creation Date:
2024-05-06 @ 8:16 PM
Last Modification Date:
2024-10-26 @ 3:24 PM
Study NCT ID:
NCT06317805
Status:
RECRUITING
Last Update Posted:
2024-03-19
First Post:
2024-02-20
Brief Title:
Initial Triple Therapy Including Parenteral Treprostinil vs Initial Double Oral Therapy in PAH Group I Patients
Sponsor:
AOP Orphan Pharmaceuticals AG
Organization:
AOP Orphan Pharmaceuticals AG
Study Overview
Official Title:
Randomized Trial Comparing Efficacy and Safety of Initial Triple Therapy Including Parenteral Treprostinil to Initial Double Oral Therapy in Pulmonary Arterial Hypertension PAH Group I Patients TripleTRE
Status:
RECRUITING
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
TripleTRE
Brief Summary:
TripleTRE investigates the effect of initial triple combination therapy oral endothelin receptor antagonist ERA oral phosphodiesterase tyüe-5 inhibitor PDE-5i parenteral treprostinil compared to double oral therapy oral ERA oral PDE-5i in pulmonary arterial hypertension PAH patients group I with intermediate-high risk or patients with intermediate-low risk with severe hemodynamic impairment at baseline in a prospective randomized unblinded setting with scope of increasing evidence for optimization of therapy concepts in PAH
The effect of initial triple combination therapy vs initial double oral therapy standard of care SoC will be measured by primary endpoint nonresponse to the assigned treatment
The effect of initial triple combination therapy vs initial double oral therapy standard of care SoC will be measured by primary endpoint nonresponse to the assigned treatment
Detailed Description:
TripleTRE is prospective randomized two-arm open-label low-interventional phase IV multi-centre clinical trial comparing efficacy and safety of initial triple therapy including parenteral treprostinil to initial double oral therapy standard of care SoC by proportion of patients achieving low risk status according to the simplified four-strata risk-assessment tool from week 24 up to 48 weeks in 110 55group treatment-naïve adult intermediate-high risk or intermediate-low risk participants with severe hemodynamic impairment with pulmonary arterial hypertension PAH group I Severe hemodynamic impairment is defined in current European Society of Cardiology ESCEuropean Respiratory Society ERS Guidelines as at least one of following conditions mean right atrial pressure RAP 20 mmHg cardiac index CI 20 Lmin stroke volume index SVI 31 mLm2 andor pulmonary vascular resistance PVR 12 WU Risk status will be assessed with the simplified four-strata risk-assessment tool as per ESCERS Guidelines for the diagnosis and treatment of pulmonary hypertension 2022
TripleTRE will be performed in adult participants with a confirmed diagnosis of idiopathic PAH IPAH hereditary PAH HPAH drug and toxin-induced PAH DPAH PAH associated with Connective Tissue Disease PAH-CTD and PAH with corrected congenital heart disease PAH-CHD
Participants will be randomized to one of the two treatment arms in 11 ratio All patients will start with double oral background medication endothelin receptor antagonist ERA and phosphodiesterase type-5 inhibitor PDE-5i Choice of double oral drug combination underline the discretion of the investigator and applicable treatment guidelines In both treatment arms all drugs ie background medication in double oral group background medication and parenteral treprostinil in initial triple group will be initiated within 3 weeks after randomization Patients randomized to treprostinil arm will receive training on infusion pump and medication after that investigational medicinal product will be handed out All patients will be handed out diaries for documentation of treprostinil dose and used vials
Primary objective of TripleTRE is to investigate the effect of initial triple combination therapy compared to initial double oral therapy on risk status The effect of initial triple combination therapy vs initial double oral therapy SoC will be measured by primary endpoint nonresponse to the assigned treatment whereas therapy respondersnon-responders are defined as
1 Therapy-responder achievement of low-risk status between week 24 and week 48
2 Therapy-non-responder
1 pulmonary hypertension PH related deterioration to high-risk status lung transplantation or death between week 12 and week 48 andor
2 additional medication or change of initial PH specific medication due to unsatisfactory efficacy between week 12 and week 48 andor
3 low risk status not achieved up to week 48
Risk status is assessed with the simplified four-strata risk-assessment tool as per ESCERS Guidelines for the diagnosis and treatment of pulmonary hypertension 2022
Commonly used variables such as hemodynamics echocardiogram ECHO and time to clinical worsening will be evaluated as secondary endpoints In addition the emPHasis-10 questionnaire will be used as disease specific and validated patient-reported outcome tool for PAH patients The European Quality of Life 5 Dimensions 5 Level Version EQ-5D-5L will be used as general patient-reported outcome tool independent from disease
TripleTRE trial is organized as a low-intervention trial consistent with definition in Clinical Trial Regulation Regulation EU No 5362014 Participants will not undergo any invasive examinations or laboratory evaluations diagnostic or monitoring procedures specifically for the purposes of this trial that would expose them to increased risk compared to standard of care Trial-related procedures as well as the frequency of assessments are in alignment with ESCERS Guidelines for the diagnosis and treatment of pulmonary hypertension 2022 and are not expected to pose additional risks to patients
Planned trial duration per patient is minimum 12 weeks and maximum 48 weeks with up to 10 visits depending on achievement of therapy responder ie low risk status or therapy non-responder status The visits 2 and 3 can be performed on phone Other visits will be performed on-site The trial will only be conducted in countries where ERA and PDE-5i treatments are standard of care and treprostinil is available to patients At the end of trial patients will be treated according to routine medical care at the PH expert centers receiving locally reimbursed medications Approximately 10 countries and 20 sites are planed
Statistical considerations
The complete statistical analysis plan SAP was finalized before first patient in FPI in meaning of first act of recruitment A one-sided Boschloo exact test at 25 significance level will be used to test the following primary hypothesis
H0 Proportion of patients achieving low risk status therapy responders between week 24 and week 48 after baseline in the initial Triple treatment group is less or equal to the proportion of patients achieving low risk status between week 24 and week 48 after baseline in the initial Double oral treatment group
The null hypothesis will be rejected if the 975 CI of the difference of proportions of therapy responders triple minus double is greater than 0
To account for the variable time on treatment of therapy responders a secondary sensitivity analysis will be performed by comparing the median time to the achievement of the low-risk status between the treatment groups
Further sensitivity and subgroup analyses are defined in detail the statistical analysis plan SAP including the handling of missing values
TripleTRE will be performed in adult participants with a confirmed diagnosis of idiopathic PAH IPAH hereditary PAH HPAH drug and toxin-induced PAH DPAH PAH associated with Connective Tissue Disease PAH-CTD and PAH with corrected congenital heart disease PAH-CHD
Participants will be randomized to one of the two treatment arms in 11 ratio All patients will start with double oral background medication endothelin receptor antagonist ERA and phosphodiesterase type-5 inhibitor PDE-5i Choice of double oral drug combination underline the discretion of the investigator and applicable treatment guidelines In both treatment arms all drugs ie background medication in double oral group background medication and parenteral treprostinil in initial triple group will be initiated within 3 weeks after randomization Patients randomized to treprostinil arm will receive training on infusion pump and medication after that investigational medicinal product will be handed out All patients will be handed out diaries for documentation of treprostinil dose and used vials
Primary objective of TripleTRE is to investigate the effect of initial triple combination therapy compared to initial double oral therapy on risk status The effect of initial triple combination therapy vs initial double oral therapy SoC will be measured by primary endpoint nonresponse to the assigned treatment whereas therapy respondersnon-responders are defined as
1 Therapy-responder achievement of low-risk status between week 24 and week 48
2 Therapy-non-responder
1 pulmonary hypertension PH related deterioration to high-risk status lung transplantation or death between week 12 and week 48 andor
2 additional medication or change of initial PH specific medication due to unsatisfactory efficacy between week 12 and week 48 andor
3 low risk status not achieved up to week 48
Risk status is assessed with the simplified four-strata risk-assessment tool as per ESCERS Guidelines for the diagnosis and treatment of pulmonary hypertension 2022
Commonly used variables such as hemodynamics echocardiogram ECHO and time to clinical worsening will be evaluated as secondary endpoints In addition the emPHasis-10 questionnaire will be used as disease specific and validated patient-reported outcome tool for PAH patients The European Quality of Life 5 Dimensions 5 Level Version EQ-5D-5L will be used as general patient-reported outcome tool independent from disease
TripleTRE trial is organized as a low-intervention trial consistent with definition in Clinical Trial Regulation Regulation EU No 5362014 Participants will not undergo any invasive examinations or laboratory evaluations diagnostic or monitoring procedures specifically for the purposes of this trial that would expose them to increased risk compared to standard of care Trial-related procedures as well as the frequency of assessments are in alignment with ESCERS Guidelines for the diagnosis and treatment of pulmonary hypertension 2022 and are not expected to pose additional risks to patients
Planned trial duration per patient is minimum 12 weeks and maximum 48 weeks with up to 10 visits depending on achievement of therapy responder ie low risk status or therapy non-responder status The visits 2 and 3 can be performed on phone Other visits will be performed on-site The trial will only be conducted in countries where ERA and PDE-5i treatments are standard of care and treprostinil is available to patients At the end of trial patients will be treated according to routine medical care at the PH expert centers receiving locally reimbursed medications Approximately 10 countries and 20 sites are planed
Statistical considerations
The complete statistical analysis plan SAP was finalized before first patient in FPI in meaning of first act of recruitment A one-sided Boschloo exact test at 25 significance level will be used to test the following primary hypothesis
H0 Proportion of patients achieving low risk status therapy responders between week 24 and week 48 after baseline in the initial Triple treatment group is less or equal to the proportion of patients achieving low risk status between week 24 and week 48 after baseline in the initial Double oral treatment group
The null hypothesis will be rejected if the 975 CI of the difference of proportions of therapy responders triple minus double is greater than 0
To account for the variable time on treatment of therapy responders a secondary sensitivity analysis will be performed by comparing the median time to the achievement of the low-risk status between the treatment groups
Further sensitivity and subgroup analyses are defined in detail the statistical analysis plan SAP including the handling of missing values
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2023-504351-26-01 | CTIS | None | None |