Trial Outcomes & Findings for Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure (NCT NCT00585546)

NCT ID: NCT00585546

Last Updated: 2017-12-15

Results Overview

• Recruitment status: TERMINATED
• Study phase: PHASE1
• Target enrollment: 18 participants
• Primary outcome timeframe: One year after LVAD explant or until transplant or death (if not explanted)
• Results posted on: 2017-12-15

Participant Flow

Of 19 consented, 1 was a screen fail and did not enter the study protocol.

Participant milestones

Measure	LVAD and (Intended) Clenbuterol Participants, all of whom received LVAD implantation, were to begin clenbuterol treatment 12 weeks after their implantation. Clenbuterol 20 mcg tablets uptitrated from 20 mcg PO TID to a maximally tolerated dose not to exceed 700 mcg PO TID. Patients will then be switched to the equivalent dose of clenbuterol liquid 59 mcg/ml PO TID. Clenbuterol will be administered for a minimum of 3 months and a maximum of 12 months.
LVAD Implantation Required for 4 Months STARTED	18
LVAD Implantation Required for 4 Months COMPLETED	13
LVAD Implantation Required for 4 Months NOT COMPLETED	5
Clenbuterol Treatment - up to 12 Months STARTED	13
Clenbuterol Treatment - up to 12 Months COMPLETED	9
Clenbuterol Treatment - up to 12 Months NOT COMPLETED	4

Reasons for withdrawal

Measure	LVAD and (Intended) Clenbuterol Participants, all of whom received LVAD implantation, were to begin clenbuterol treatment 12 weeks after their implantation. Clenbuterol 20 mcg tablets uptitrated from 20 mcg PO TID to a maximally tolerated dose not to exceed 700 mcg PO TID. Patients will then be switched to the equivalent dose of clenbuterol liquid 59 mcg/ml PO TID. Clenbuterol will be administered for a minimum of 3 months and a maximum of 12 months.
Clenbuterol Treatment - up to 12 Months Death	1
Clenbuterol Treatment - up to 12 Months Adverse Event	3

Baseline Characteristics

Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure

Baseline characteristics by cohort

Measure	LVAD and Clenbuterol n=18 Participants clenbuterol: Clenbuterol 20 mcg tablets uptitrated from 20 mcg PO TID to a maximally tolerated dose not to exceed 700 mcg PO TID. Patients will then be switched to the equivalent dose of clenbuterol liquid 59 mcg/ml PO TID. Clenbuterol will be administered for a minimum of 3 months and a maximum of 12 months.
Age, Continuous	57 years n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants
Region of Enrollment United States	18 participants n=5 Participants

PRIMARY outcome

Timeframe: One year after LVAD explant or until transplant or death (if not explanted)

Outcome measures

Measure	LVAD and Clenbuterol n=18 Participants clenbuterol: Clenbuterol 20 mcg tablets uptitrated from 20 mcg PO TID to a maximally tolerated dose not to exceed 700 mcg PO TID. Patients will then be switched to the equivalent dose of clenbuterol liquid 59 mcg/ml PO TID. Clenbuterol will be administered for a minimum of 3 months and a maximum of 12 months.
Percent of Subjects Who Experience LVAD Removal and Subsequent Freedom From Mechanical Circulatory Support or Heart Transplantation for 1-year After Explantation	5.6 percentage of participants

SECONDARY outcome

Timeframe: Maximum 12 months after LVAD implantation

Population: Because only 13 began Clenbuterol, only 13 are "evaluable" for this purpose.

Outcome measures

Measure	LVAD and Clenbuterol n=13 Participants clenbuterol: Clenbuterol 20 mcg tablets uptitrated from 20 mcg PO TID to a maximally tolerated dose not to exceed 700 mcg PO TID. Patients will then be switched to the equivalent dose of clenbuterol liquid 59 mcg/ml PO TID. Clenbuterol will be administered for a minimum of 3 months and a maximum of 12 months.
The Number of Evaluable Subjects Meeting Explant Criteria and Subsequently Explanted	1 Participants

SECONDARY outcome

Timeframe: Up to 16 months after LVAD implantation (12 months after beginning clenbuterol)

Outcome measures

Measure	LVAD and Clenbuterol n=13 Participants clenbuterol: Clenbuterol 20 mcg tablets uptitrated from 20 mcg PO TID to a maximally tolerated dose not to exceed 700 mcg PO TID. Patients will then be switched to the equivalent dose of clenbuterol liquid 59 mcg/ml PO TID. Clenbuterol will be administered for a minimum of 3 months and a maximum of 12 months.
Number of Subjects Who Received Maximum Target Dose of Clenbuterol	13 Participants

SECONDARY outcome

Timeframe: Time to explant (but not to be followed for more than 16 months)

Time from LVAD placement to explant for the single participant who achieved explant

Outcome measures

Measure	LVAD and Clenbuterol n=1 Participants clenbuterol: Clenbuterol 20 mcg tablets uptitrated from 20 mcg PO TID to a maximally tolerated dose not to exceed 700 mcg PO TID. Patients will then be switched to the equivalent dose of clenbuterol liquid 59 mcg/ml PO TID. Clenbuterol will be administered for a minimum of 3 months and a maximum of 12 months.
Time to Device Explant for Subjects Meeting Explant Criteria Defined in the Protocol	28 weeks

SECONDARY outcome

Timeframe: 18 months after explantation

Outcome measures

Measure	LVAD and Clenbuterol n=1 Participants clenbuterol: Clenbuterol 20 mcg tablets uptitrated from 20 mcg PO TID to a maximally tolerated dose not to exceed 700 mcg PO TID. Patients will then be switched to the equivalent dose of clenbuterol liquid 59 mcg/ml PO TID. Clenbuterol will be administered for a minimum of 3 months and a maximum of 12 months.
Absolute Change in Left Ventricular Ejection Fraction From Explant to 18 Months Following Device Explant	-.09 absolute change in ejection fraction

SECONDARY outcome

Timeframe: Up to 8 weeks after LVAD implantation

Population: Because data only is available for 15 participants for 8 week post implant AST value, it has a different participants analyzed value

Outcome measures

Measure	LVAD and Clenbuterol n=18 Participants clenbuterol: Clenbuterol 20 mcg tablets uptitrated from 20 mcg PO TID to a maximally tolerated dose not to exceed 700 mcg PO TID. Patients will then be switched to the equivalent dose of clenbuterol liquid 59 mcg/ml PO TID. Clenbuterol will be administered for a minimum of 3 months and a maximum of 12 months.
Absolute Percent Change in Serum Creatinine and Aspartate Transaminase (AST) From Baseline to Week 8 Post Implant Creatinine	17.2 percent change Standard Deviation 15.2
Absolute Percent Change in Serum Creatinine and Aspartate Transaminase (AST) From Baseline to Week 8 Post Implant aspartate transaminase (AST)	25 percent change Standard Deviation 19.7

SECONDARY outcome

Timeframe: 1 year following LVAD implantation

Population: While baseline data was available for 13 participants at baseline, (start of clenbuterol), different numbers of participants provided evaluable data At six months post implant and 12 months, so the mean changes are based on the actual population that provided both data points as listed below

Scale 0 - 100 where 0 is worst possible health state and 100 is perfect health.

Outcome measures

Measure	LVAD and Clenbuterol n=13 Participants clenbuterol: Clenbuterol 20 mcg tablets uptitrated from 20 mcg PO TID to a maximally tolerated dose not to exceed 700 mcg PO TID. Patients will then be switched to the equivalent dose of clenbuterol liquid 59 mcg/ml PO TID. Clenbuterol will be administered for a minimum of 3 months and a maximum of 12 months.
Mean Change in EuroQoL Visual Analog Scale (EQ5D-VAS) From Baseline to 6 Months and 1 Year Following Device Implant 6 months post implant	46 units on a scale Standard Deviation 35
Mean Change in EuroQoL Visual Analog Scale (EQ5D-VAS) From Baseline to 6 Months and 1 Year Following Device Implant 12 months post implant	51 units on a scale Standard Deviation 30

SECONDARY outcome

Timeframe: 6 months following LVAD implantation

Population: Only 11 participants provided usable data at the six month time point.

Scale 0 - 105 (0- 5 on 21 items) where 0 means heart failure has not limited daily life at all and high scores mean that daily functions are greatly limited.

Outcome measures

Measure	LVAD and Clenbuterol n=11 Participants clenbuterol: Clenbuterol 20 mcg tablets uptitrated from 20 mcg PO TID to a maximally tolerated dose not to exceed 700 mcg PO TID. Patients will then be switched to the equivalent dose of clenbuterol liquid 59 mcg/ml PO TID. Clenbuterol will be administered for a minimum of 3 months and a maximum of 12 months.
Mean Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) From Baseline to 6 Months	28.3 units on a scale Standard Deviation 19.7

SECONDARY outcome

Timeframe: up to 16 months, variable based on length of time receiveing clenbuterol

Population: data is available for 9 evaluable subjects at end of clenbuterol

Outcome measures

Measure	LVAD and Clenbuterol n=9 Participants clenbuterol: Clenbuterol 20 mcg tablets uptitrated from 20 mcg PO TID to a maximally tolerated dose not to exceed 700 mcg PO TID. Patients will then be switched to the equivalent dose of clenbuterol liquid 59 mcg/ml PO TID. Clenbuterol will be administered for a minimum of 3 months and a maximum of 12 months.
Mean Change in Left Ventricular Ejection Fraction From Device Implant to Completion of Clenbuterol Therapy	0.16 ejection fraction Standard Deviation .10

SECONDARY outcome

Timeframe: baseline to week 8 post clenbuterol

Population: baseline data is based on 19 participants, but different subsequent data collections had different numbers of evaluable subjects listed below

Outcome measures

Measure	LVAD and Clenbuterol n=19 Participants clenbuterol: Clenbuterol 20 mcg tablets uptitrated from 20 mcg PO TID to a maximally tolerated dose not to exceed 700 mcg PO TID. Patients will then be switched to the equivalent dose of clenbuterol liquid 59 mcg/ml PO TID. Clenbuterol will be administered for a minimum of 3 months and a maximum of 12 months.
Absolute Percent Change in Serum Creatinine and Aspartate Transaminase (AST) From Baseline to Week 8 Post Clenbuterol creatinine from baseline to week 8 of clenbuterol	-15.8 percent change Standard Deviation 13.3
Absolute Percent Change in Serum Creatinine and Aspartate Transaminase (AST) From Baseline to Week 8 Post Clenbuterol AST from baseline to week 8 on clenbuterol	15.6 percent change Standard Deviation 14.3

SECONDARY outcome

Timeframe: 1 year

Population: Data is not available for Minnesota Living with Heart Failure Questionnaire at the 12 month time point.

Scale 0 - 105 (0- 5 on 21 items) where 0 means heart failure has not limited daily life at all and high scores mean that daily functions are greatly limited.

Outcome measures

Outcome data not reported

Adverse Events

LVAD and Clenbuterol

Serious events: 13 serious events

Other events: 11 other events

Deaths: 1 deaths

Serious adverse events

Measure	LVAD and Clenbuterol n=18 participants at risk clenbuterol: Clenbuterol 20 mcg tablets uptitrated from 20 mcg PO TID to a maximally tolerated dose not to exceed 700 mcg PO TID. Patients will then be switched to the equivalent dose of clenbuterol liquid 59 mcg/ml PO TID. Clenbuterol will be administered for a minimum of 3 months and a maximum of 12 months.
Gastrointestinal disorders Abdominal Perforation Requiring Re-Operation	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Blood and lymphatic system disorders Anemia, Pancytopenia	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Infections and infestations AV Endocarditis	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Gastrointestinal disorders Bleeding	22.2% 4/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Cardiac disorders Cardiac arrhythmia	11.1% 2/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Cardiac disorders Cardiopulmonary Arrest	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Renal and urinary disorders Dehydration	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Product Issues Device malfunction	11.1% 2/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Infections and infestations Fever	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Respiratory, thoracic and mediastinal disorders Hemoptysis	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Cardiac disorders History Afib/Flutter since XVE Implant	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Infections and infestations Infection	16.7% 3/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Infections and infestations Intermittent Fever, Pain, Leukocytosis	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Cardiac disorders Left Atrial Thrombus	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Respiratory, thoracic and mediastinal disorders Left Pleural Effusion	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Injury, poisoning and procedural complications Left Sided Pain Radiating to Axilla	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Injury, poisoning and procedural complications Left sided pneumothorax - Left Pleural CT inserted	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Gastrointestinal disorders Nausea and Vomiting	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Nervous system disorders Neurological event	16.7% 3/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Renal and urinary disorders Renal dysfunction	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Respiratory, thoracic and mediastinal disorders Respiratory failure	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Injury, poisoning and procedural complications Retropericardial Hematoma	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Respiratory, thoracic and mediastinal disorders Shortness of Breath	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Infections and infestations Viral Syndrome	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Cardiac disorders Pericardial fluid collection	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Cardiac disorders Heart Failure	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant

Other adverse events

Measure	LVAD and Clenbuterol n=18 participants at risk clenbuterol: Clenbuterol 20 mcg tablets uptitrated from 20 mcg PO TID to a maximally tolerated dose not to exceed 700 mcg PO TID. Patients will then be switched to the equivalent dose of clenbuterol liquid 59 mcg/ml PO TID. Clenbuterol will be administered for a minimum of 3 months and a maximum of 12 months.
Gastrointestinal disorders Abdominal Pain	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Gastrointestinal disorders Bleeding	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Cardiac disorders Cardiac arrhythmia	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Cardiac disorders Chest Pain	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Infections and infestations Elevated White Blood Cell/Leukocytosis	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Renal and urinary disorders Hyperkalemia	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Cardiac disorders Hypertension	11.1% 2/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Cardiac disorders Implantable Cardioverter Defibrillator (ICD) Discharge	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Infections and infestations Infection	22.2% 4/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Injury, poisoning and procedural complications Muscle Pain	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Musculoskeletal and connective tissue disorders Myalgia	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Nervous system disorders Neurological	11.1% 2/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Psychiatric disorders Psychiatric episode	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Injury, poisoning and procedural complications Severe Muscle Spasms	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Cardiac disorders Sinus Tachycardia Leading to ICD Shocks	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Cardiac disorders Hypotension	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Gastrointestinal disorders Vomiting	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant
Gastrointestinal disorders Blood Bowel Movement	5.6% 1/18 • Adverse event data was collected for approximately 24 months or up to transplant, death, or explant

Additional Information

Francis Pagani

University of Michigan

Phone: 734 647-2894

Email: fpagani@med.umich.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place