A Randomized Controlled Multicenter Trial of Exercise Training in Pulmonary Hypertension in European Countries

NCT03345212 | Completed

• 1 other identifier: EU-TRAIN-01
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic pulmonary hypertension (PH) is associated with impaired exercise capacity, quality of life and right ventricular function. The disease is characterized by an increase of pulmonary vascular resistance and pulmonary arterial pressure, leading to right heart insufficiency. Despite optimized combination-medical therapy most patients remain symptomatic, have reduced exercise capacity, quality of life and reduced survival rates, with an annual mortality rate of approximately 5 -15 % or even higher. Previous training studies have suggested that exercise training as add-on to medical treatment is highly effective improving exercise capacity, quality of life and symptoms. The current guidelines recommend exercise training only in specialized centres including both PH and rehabilitation specialists who are experienced in exercise training of severely compromised patients. A specialized PH-training program has been performed in Heidelberg since 2003 including \>1200 patients with various forms of chronic PH. The exercise training program is performed in a special setting with an in-hospital start of the rehabilitation program. It is characterized by a low-dose closely supervised exercise training in small groups with additional psychological support and mental training. This training program for patients with PH will be implemented in European centers to add exercise training to the existing PH therapies. The effect of the training on physical exercise capacity will be assessed by 6-minute walking distance (6-MWD). Further clinical parameters will be assessed to evaluate the effect on exercise capacity, quality of life and symptoms. The aim of this study is to guide European PH-centers to become specialized centers for training in PH. 126 patients will be included, who either receive exercise training or continue their daily sedentary life style (1:1 randomization) for 15 weeks. As inpatient settings are not available in all healthcare systems the training program will be adapted from the specific training program for PH patients developed in Heidelberg to a procedure, which is feasible in the local participating centres. Another objective of this study is to assess if the particular adopted training program specified for each participating centre and country is still safe and effective.

Conditions

Pulmonary Hypertension

Outcome Measures

Primary Outcomes (1)

• 6 MWD

  Change in 6-MWD between baseline and 15 weeks in the training vs. the control Group; meters

  15 weeks

Secondary Outcomes (55)

• Change in WHO functional class in training vs. control group

  15 weeks

• Change in Quality of life in training vs. control group

  15 weeks

• Change in Borg scale 6-MWD training vs. control group

  15 weeks

• Change in tricuspid annular plane systolic excursion

  15 weeks

• Change in tissue Doppler imaging

  15 weeks

Study Arms (2)

Control group

NO INTERVENTION

Patients in this group continue their sedentary life-style throughout the study period. Patients will be advised to perform no specific exercise training during the trial. After 15 weeks, the patients are offered to take part in the training program as well.

Training group

EXPERIMENTAL

Standard rehabilitation therapy includes dietary measures, massages and relaxation techniques. Additionally, patients perform exercise and respiratory therapy and mental gait training. Patients will be informed about group allocation.

Other: Exercise training

Interventions

Exercise training OTHER

The rehabilitation program comprises interval ergometer training, dumbbell training, respiratory therapy, mental training and guided walks for 5-7 times/week.

Training group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female and male patients of any ethnic origin ≥ 18 years
• WHO functional class II-IV
• PH diagnosed by right heart catheter showing:
• Baseline mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg
• Baseline pulmonary vascular resistance (PVR) ≥ 240 dyn x s x cm-5
• Baseline pulmonary capillary wedge pressure (PCWP) ≤ 15 mm Hg
• Patients receiving optimized conventional PH therapy including intensified treatment with diuretics and who have been stable for 2 months before entering the study
• Except for diuretics, medical treatment should not be expected to change during the entire 15-week study period
• Negative pregnancy test (β-HCG) at the start of the trial and appropriate contraception throughout the study for women with child-bearing potential
• Able to understand and willing to sign the Informed Consent Form

You may not qualify if:

• PH of any cause other than permitted in the entry criteria, e.g. concomitantly to portal hypertension, complex congenital heart disease, reversed shunt, HIV infection, suspected pulmonary veno-occlusive disease based on pulmonary edema during a previous vasoreactivity test or on abnormal findings compatible with that diagnosis (septal lines or pulmonary edema at high resolution computer tomography), congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to pulmonary hypertension or unclear diagnosis
• Pregnancy
• Patients with signs of right heart decompensation
• Walking disability
• Acute infection
• Pyrexia
• Any change in disease-targeted therapy within the last 2 months
• Any subject who is scheduled to receive an investigational drug during the course of this study
• Severe lung disease: FEV1/FVC \<0.5 and total lung capacity \< 70% of the normal value
• Active liver disease, porphyria or elevations of serum transaminases \>3 x ULN (upper limit of normal) or bilirubin \> 1.5 x ULN
• Hemoglobin concentration of less than 75 % of the lower limit of normal
• Systolic blood pressure \< 85 mmHg
• Active myocarditis, instable angina pectoris, exercise induced ventricular arrhythmias, decompensated heart failure, hypertrophic obstructive cardiomyopathy, highly impaired left ventricular function
• History or suspicion of inability to cooperate adequately. will be excluded from the study.
• Acute psychosis or other states of mind, which seem to impair patient's ability to comprehend instructions

Sponsors & Collaborators

• Heidelberg University: lead

Study Sites (1)

Centre for pulmonary hypertension of the Thoraxclinic at the University Hospital Heidelberg

Heidelberg, 69126, Germany

Location

Related Publications (9)

• Mereles D, Ehlken N, Kreuscher S, Ghofrani S, Hoeper MM, Halank M, Meyer FJ, Karger G, Buss J, Juenger J, Holzapfel N, Opitz C, Winkler J, Herth FF, Wilkens H, Katus HA, Olschewski H, Grunig E. Exercise and respiratory training improve exercise capacity and quality of life in patients with severe chronic pulmonary hypertension. Circulation. 2006 Oct 3;114(14):1482-9. doi: 10.1161/CIRCULATIONAHA.106.618397. Epub 2006 Sep 18.

  PMID: 16982941 BACKGROUND

• Grunig E, Ehlken N, Ghofrani A, Staehler G, Meyer FJ, Juenger J, Opitz CF, Klose H, Wilkens H, Rosenkranz S, Olschewski H, Halank M. Effect of exercise and respiratory training on clinical progression and survival in patients with severe chronic pulmonary hypertension. Respiration. 2011;81(5):394-401. doi: 10.1159/000322475. Epub 2011 Feb 9.

  PMID: 21311162 BACKGROUND

• Grunig E, Lichtblau M, Ehlken N, Ghofrani HA, Reichenberger F, Staehler G, Halank M, Fischer C, Seyfarth HJ, Klose H, Meyer A, Sorichter S, Wilkens H, Rosenkranz S, Opitz C, Leuchte H, Karger G, Speich R, Nagel C. Safety and efficacy of exercise training in various forms of pulmonary hypertension. Eur Respir J. 2012 Jul;40(1):84-92. doi: 10.1183/09031936.00123711. Epub 2012 Feb 9.

  PMID: 22323570 BACKGROUND

• Grunig E, Maier F, Ehlken N, Fischer C, Lichtblau M, Blank N, Fiehn C, Stockl F, Prange F, Staehler G, Reichenberger F, Tiede H, Halank M, Seyfarth HJ, Wagner S, Nagel C. Exercise training in pulmonary arterial hypertension associated with connective tissue diseases. Arthritis Res Ther. 2012 Jun 18;14(3):R148. doi: 10.1186/ar3883.

  PMID: 22709477 BACKGROUND

• Nagel C, Prange F, Guth S, Herb J, Ehlken N, Fischer C, Reichenberger F, Rosenkranz S, Seyfarth HJ, Mayer E, Halank M, Grunig E. Exercise training improves exercise capacity and quality of life in patients with inoperable or residual chronic thromboembolic pulmonary hypertension. PLoS One. 2012;7(7):e41603. doi: 10.1371/journal.pone.0041603. Epub 2012 Jul 25.

  PMID: 22848542 BACKGROUND

• Becker-Grunig T, Klose H, Ehlken N, Lichtblau M, Nagel C, Fischer C, Gorenflo M, Tiede H, Schranz D, Hager A, Kaemmerer H, Miera O, Ulrich S, Speich R, Uiker S, Grunig E. Efficacy of exercise training in pulmonary arterial hypertension associated with congenital heart disease. Int J Cardiol. 2013 Sep 20;168(1):375-81. doi: 10.1016/j.ijcard.2012.09.036. Epub 2012 Oct 5.

  PMID: 23041100 BACKGROUND

• Halank M, Einsle F, Lehman S, Bremer H, Ewert R, Wilkens H, Meyer FJ, Grunig E, Seyfarth HJ, Kolditz M, Wieder G, Hoffken G, Kollner V. Exercise capacity affects quality of life in patients with pulmonary hypertension. Lung. 2013 Aug;191(4):337-43. doi: 10.1007/s00408-013-9472-6. Epub 2013 May 17.

  PMID: 23681593 BACKGROUND

• Kabitz HJ, Bremer HC, Schwoerer A, Sonntag F, Walterspacher S, Walker DJ, Ehlken N, Staehler G, Windisch W, Grunig E. The combination of exercise and respiratory training improves respiratory muscle function in pulmonary hypertension. Lung. 2014 Apr;192(2):321-8. doi: 10.1007/s00408-013-9542-9. Epub 2013 Dec 13.

  PMID: 24338088 BACKGROUND

• Ehlken N, Lichtblau M, Klose H, Weidenhammer J, Fischer C, Nechwatal R, Uiker S, Halank M, Olsson K, Seeger W, Gall H, Rosenkranz S, Wilkens H, Mertens D, Seyfarth HJ, Opitz C, Ulrich S, Egenlauf B, Grunig E. Exercise training improves peak oxygen consumption and haemodynamics in patients with severe pulmonary arterial hypertension and inoperable chronic thrombo-embolic pulmonary hypertension: a prospective, randomized, controlled trial. Eur Heart J. 2016 Jan 1;37(1):35-44. doi: 10.1093/eurheartj/ehv337. Epub 2015 Jul 31.

  PMID: 26231884 BACKGROUND

MeSH Terms

Conditions

Hypertension, Pulmonary

Interventions

Exercise

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Ekkehard Grünig, MD

  Centre for pulmonary hypertension of the Thoraxclinic at the University Hospital Heidelberg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: July 27, 2017
• First Posted: November 17, 2017
• Study Start: February 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2019
• Last Updated: December 19, 2019

Record last verified: 2019-12

Locations

DE (1)