Finding the Optimum Regimen for Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy Clinical Trial

— FOR-DMD  

Official title:

Duchenne Muscular Dystrophy: Double-blind Randomized Trial to Find Optimum Steroid Regimen

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01603407
• Other study ID #: U01NS061799
• Secondary ID: 2010-023744-33U0
• Status: Completed
• Phase: Phase 3
• Start date: January 2013
• Est. completion date: November 2019

Study information

• Verified date: August 2022
• Source: University of Rochester
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The Finding the Optimum Regimen for Duchenne Muscular Dystrophy (FOR DMD) study will compare three ways of giving corticosteroids to boys with Duchenne muscular dystrophy (DMD) to determine which of the three ways increases muscle strength the most, and which causes the fewest side effects. Using the results of this study, the investigators aim to provide patients and families with clearer information about the best way to take these drugs.

Description:

Boys with Duchenne muscular dystrophy experience progressive muscle weakness as they grow up. Corticosteroids are currently the only medicine that has been shown to increase muscle strength in boys with DMD. Benefits include an increase in the length of time that boys could continue to walk, reduction in the development of curvature of the spine, a longer time of adequate breathing, and possible protection against the development of heart problems.

Doctors have tried different ways of prescribing corticosteroids in order to decrease undesirable side effects of the drug. No controlled, long-term study has ever looked at the effects of different corticosteroids to see which one improves strength the most and which one causes the fewest side effects, over a period of time. Different doctors in different countries prescribe the drugs in different ways, and some do not prescribe corticosteroids at all.

The FOR DMD study will enroll boys with DMD ages 4-7. The study will look at three ways of taking the following corticosteroids by the mouth to determine which increases muscle strength the most, and which causes the fewest side effects:

1. Prednisone 0.75mg/kg/day

2. Prednisone 0.75mg/kg/day switching between 10 days on and 10 days off treatment

3. Deflazacort 0.9mg/kg/day.

The study will take place at 40 academic medical centers in the United States, Canada, United Kingdom, Germany and Italy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 196
• Est. completion date: November 2019
• Est. primary completion date: November 2019
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 4 Years to 7 Years

Eligibility

Inclusion Criteria:

• Evidence of signed and dated informed consent form.

• Confirmed diagnosis of Duchenne muscular dystrophy

• Age greater than or equal to 4 years and less than 8 years old

• Ability to rise independently from floor, from supine to standing

• Willingness and ability to comply with scheduled visits, drug administration plan and study procedures

• Ability to maintain reproducible FVC measurements.

Exclusion Criteria:

• History of major renal or hepatic impairment, immunosuppression or other contraindications to corticosteroid therapy.

• History of chronic systemic fungal or viral infections. Acute bacterial infection(including TB) would exclude from enrolment until the infection had been appropriately treated and resolved.

• Diabetes mellitus.

• Idiopathic hypercalcuria.

• Lack of chicken pox immunity and refusal to undergo immunization.

• Evidence of symptomatic cardiomyopathy at screening assessment (one to three months prior to the baseline visit). Asymptomatic cardiac abnormality on investigation would not be an exclusion.

• Current or previous treatment (greater than four consecutive weeks of oral therapy) with corticosteroids or other immunosuppressive treatments for DMD or other recurrent indications (e.g., asthma), unless approved by FOR-DMD Team (i.e., concurrent participation in another allowed DMD trial).

• Inability to take tablets, as assessed by the site investigator by the end of the screening period (the screening period ranges from one to three months prior to the baseline visit).

• Allergy/sensitivity to study drugs or their formulations including lactose and/or sucrose intolerance.

• Severe behavioral problems, including severe autism.

• Previous or ongoing medical condition, medical history, physical findings or laboratory abnormalities that could affect safety, make it unlikely that treatment and follow up will be correctly completed or impair the assessment of study results, in the judgment of the site investigator.

• Weight of less than 13 kilograms.

• Exposure to any investigational drug currently or within 3 months prior to start of study treatment.

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• Prednisone
daily prednisone (0.75 mg/kg/day) tablets for 36-60 months
• Prednisone
intermittent prednisone (0.75 mg/kg/day, 10 days on, 10 days off) tablets for 36 to 60 months
• Deflazacort
daily deflazacort (0.9 mg/kg/day) tablets for 36-60 months

Locations

Country	Name	City	State
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	Children's Hospital London Health Sciences Centre	London	Ontario
Canada	Children's Hospital of Eastern Ontario (CHEO)	Ottawa	Ontario
Germany	Children's Hospital, Technical University Dresden	Dresden
Germany	University Hospital of Essen	Essen
Germany	University Medical Center Freiburg	Freiburg
Germany	Children's University Hospital, Göttingen	Göttingen
Italy	University of Messina AOU Policlinico Gaetano Martino	Messina
Italy	C. Besta Neurological Institute Foundation	Milan
Italy	University of Padova School of Medicine	Padova
Italy	Neuromuscular Center University of Turin	Torino
United Kingdom	Heart of England NHS Foundation Trust Birmingham Heartland's Hospital	Birmingham
United Kingdom	Greater Glasgow and Clyde NHS Yorkhill Hospital	Glasgow	Scotland
United Kingdom	The General Infirmary at Leeds	Leeds	England
United Kingdom	Alder Hey Children's Hospital NHS Trust	Liverpool
United Kingdom	Great Ormond Street Hospital for Children NHS Trust	London
United Kingdom	Royal Manchester Children's Hospital	Manchester
United Kingdom	Institute of Human Genetics, International Centre for Life	Newcastle Upon Tyne
United States	University of New Mexico Health Science Center	Albuquerque	New Mexico
United States	Boston Children's Hospital	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Ann and Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of California Los Angeles (UCLA) Medical Center	Los Angeles	California
United States	Vanderbilt Children's Hospital	Nashville	Tennessee
United States	Nemours Children's Hospital	Orlando	Florida
United States	University of Rochester Medical Center	Rochester	New York
United States	University of California Davis Medical Center	Sacramento	California
United States	University of Utah Medical Center	Salt Lake City	Utah
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (4)

Lead Sponsor	Collaborator
University of Rochester	National Institute of Neurological Disorders and Stroke (NINDS), Newcastle University, University Medical Center Freiburg

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Italy,  United Kingdom, 

References & Publications (56)

Angelini C, Pegoraro E, Turella E, Intino MT, Pini A, Costa C. Deflazacort in Duchenne dystrophy: study of long-term effect. Muscle Nerve. 1994 Apr;17(4):386-91. Erratum in: Muscle Nerve 1994 Jul;17(7):833. — View Citation

Atkinson MJ, Sinha A, Hass SL, Colman SS, Kumar RN, Brod M, Rowland CR. Validation of a general measure of treatment satisfaction, the Treatment Satisfaction Questionnaire for Medication (TSQM), using a national panel study of chronic disease. Health Qual Life Outcomes. 2004 Feb 26;2:12. — View Citation

Bäckman E, Henriksson KG. Low-dose prednisolone treatment in Duchenne and Becker muscular dystrophy. Neuromuscul Disord. 1995 May;5(3):233-41. — View Citation

Bianchi ML. How to manage osteoporosis in children. Best Pract Res Clin Rheumatol. 2005 Dec;19(6):991-1005. Review. — View Citation

Biggar WD, Bachrach LK, Henderson RC, Kalkwarf H, Plotkin H, Wong BL. Bone health in Duchenne muscular dystrophy: a workshop report from the meeting in Cincinnati, Ohio, July 8, 2004. Neuromuscul Disord. 2005 Jan;15(1):80-5. — View Citation

Biggar WD, Gingras M, Fehlings DL, Harris VA, Steele CA. Deflazacort treatment of Duchenne muscular dystrophy. J Pediatr. 2001 Jan;138(1):45-50. — View Citation

Biggar WD, Harris VA, Eliasoph L, Alman B. Long-term benefits of deflazacort treatment for boys with Duchenne muscular dystrophy in their second decade. Neuromuscul Disord. 2006 Apr;16(4):249-55. Epub 2006 Mar 20. — View Citation

Biggar WD, Politano L, Harris VA, Passamano L, Vajsar J, Alman B, Palladino A, Comi LI, Nigro G. Deflazacort in Duchenne muscular dystrophy: a comparison of two different protocols. Neuromuscul Disord. 2004 Sep;14(8-9):476-82. — View Citation

Brooke MH, Fenichel GM, Griggs RC, Mendell JR, Moxley R, Florence J, King WM, Pandya S, Robison J, Schierbecker J, et al. Duchenne muscular dystrophy: patterns of clinical progression and effects of supportive therapy. Neurology. 1989 Apr;39(4):475-81. — View Citation

Brooke MH, Fenichel GM, Griggs RC, Mendell JR, Moxley R, Miller JP, Province MA. Clinical investigation in Duchenne dystrophy: 2. Determination of the "power" of therapeutic trials based on the natural history. Muscle Nerve. 1983 Feb;6(2):91-103. — View Citation

Brooke MH, Fenichel GM, Griggs RC, Mendell JR, Moxley RT 3rd, Miller JP, Kaiser KK, Florence JM, Pandya S, Signore L, et al. Clinical investigation of Duchenne muscular dystrophy. Interesting results in a trial of prednisone. Arch Neurol. 1987 Aug;44(8):812-7. — View Citation

Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, Shapiro F, Tomezsko J, Constantin C; DMD Care Considerations Working Group. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 2010 Jan;9(1):77-93. doi: 10.1016/S1474-4422(09)70271-6. Epub 2009 Nov 27. Review. — View Citation

Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, Shapiro F, Tomezsko J, Constantin C; DMD Care Considerations Working Group. Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care. Lancet Neurol. 2010 Feb;9(2):177-89. doi: 10.1016/S1474-4422(09)70272-8. Epub 2009 Nov 27. Review. Erratum in: Lancet Neurol. 2010 Mar;9(3):237. — View Citation

Bushby K, Muntoni F, Bourke JP. 107th ENMC international workshop: the management of cardiac involvement in muscular dystrophy and myotonic dystrophy. 7th-9th June 2002, Naarden, the Netherlands. Neuromuscul Disord. 2003 Feb;13(2):166-72. — View Citation

Bushby K, Muntoni F, Urtizberea A, Hughes R, Griggs R. Report on the 124th ENMC International Workshop. Treatment of Duchenne muscular dystrophy; defining the gold standards of management in the use of corticosteroids. 2-4 April 2004, Naarden, The Netherlands. Neuromuscul Disord. 2004 Sep;14(8-9):526-34. — View Citation

Carter GT, McDonald CM. Preserving function in Duchenne dystrophy with long-term pulse prednisone therapy. Am J Phys Med Rehabil. 2000 Sep-Oct;79(5):455-8. — View Citation

Collett BR, Ohan JL, Myers KM. Ten-year review of rating scales. V: scales assessing attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2003 Sep;42(9):1015-37. Review. — View Citation

Collett BR, Ohan JL, Myers KM. Ten-year review of rating scales. VI: scales assessing externalizing behaviors. J Am Acad Child Adolesc Psychiatry. 2003 Oct;42(10):1143-70. Review. — View Citation

Connolly AM, Schierbecker J, Renna R, Florence J. High dose weekly oral prednisone improves strength in boys with Duchenne muscular dystrophy. Neuromuscul Disord. 2002 Dec;12(10):917-25. — View Citation

Duboc D, Meune C, Lerebours G, Devaux JY, Vaksmann G, Bécane HM. Effect of perindopril on the onset and progression of left ventricular dysfunction in Duchenne muscular dystrophy. J Am Coll Cardiol. 2005 Mar 15;45(6):855-7. — View Citation

Dubowitz V, Kinali M, Main M, Mercuri E, Muntoni F. Remission of clinical signs in early duchenne muscular dystrophy on intermittent low-dosage prednisolone therapy. Eur J Paediatr Neurol. 2002;6(3):153-9. — View Citation

Eagle M, Baudouin SV, Chandler C, Giddings DR, Bullock R, Bushby K. Survival in Duchenne muscular dystrophy: improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Neuromuscul Disord. 2002 Dec;12(10):926-9. — View Citation

Fenichel GM, Florence JM, Pestronk A, Mendell JR, Moxley RT 3rd, Griggs RC, Brooke MH, Miller JP, Robison J, King W, et al. Long-term benefit from prednisone therapy in Duchenne muscular dystrophy. Neurology. 1991 Dec;41(12):1874-7. — View Citation

Fenichel GM, Mendell JR, Moxley RT 3rd, Griggs RC, Brooke MH, Miller JP, Pestronk A, Robison J, King W, Signore L, et al. A comparison of daily and alternate-day prednisone therapy in the treatment of Duchenne muscular dystrophy. Arch Neurol. 1991 Jun;48(6):575-9. — View Citation

Follmann D. Multivariate tests for multiple endpoints in clinical trials. Stat Med. 1995 Jun 15;14(11):1163-75. Review. — View Citation

Griggs RC, Moxley RT 3rd, Mendell JR, Fenichel GM, Brooke MH, Pestronk A, Miller JP, Cwik VA, Pandya S, Robison J, et al. Duchenne dystrophy: randomized, controlled trial of prednisone (18 months) and azathioprine (12 months). Neurology. 1993 Mar;43(3 Pt 1):520-7. — View Citation

Griggs RC, Moxley RT 3rd, Mendell JR, Fenichel GM, Brooke MH, Pestronk A, Miller JP. Prednisone in Duchenne dystrophy. A randomized, controlled trial defining the time course and dose response. Clinical Investigation of Duchenne Dystrophy Group. Arch Neurol. 1991 Apr;48(4):383-8. — View Citation

Hinton VJ, Nereo NE, Fee RJ, Cyrulnik SE. Social behavior problems in boys with Duchenne muscular dystrophy. J Dev Behav Pediatr. 2006 Dec;27(6):470-6. — View Citation

Hopke PK, Liu C, Rubin DB. Multiple imputation for multivariate data with missing and below-threshold measurements: time-series concentrations of pollutants in the Arctic. Biometrics. 2001 Mar;57(1):22-33. — View Citation

Kinali M, Mercuri E, Main M, Muntoni F, Dubowitz V. An effective, low-dosage, intermittent schedule of prednisolone in the long-term treatment of early cases of Duchenne dystrophy. Neuromuscul Disord. 2002 Oct;12 Suppl 1:S169-74. — View Citation

Lippuner K, Casez JP, Horber FF, Jaeger P. Effects of deflazacort versus prednisone on bone mass, body composition, and lipid profile: a randomized, double blind study in kidney transplant patients. J Clin Endocrinol Metab. 1998 Nov;83(11):3795-802. — View Citation

Little R, Yau L. Intent-to-treat analysis for longitudinal studies with drop-outs. Biometrics. 1996 Dec;52(4):1324-33. — View Citation

Loftus J, Allen R, Hesp R, David J, Reid DM, Wright DJ, Green JR, Reeve J, Ansell BM, Woo PM. Randomized, double-blind trial of deflazacort versus prednisone in juvenile chronic (or rheumatoid) arthritis: a relatively bone-sparing effect of deflazacort. Pediatrics. 1991 Sep;88(3):428-36. — View Citation

Lunceford JK, Davidian M. Stratification and weighting via the propensity score in estimation of causal treatment effects: a comparative study. Stat Med. 2004 Oct 15;23(19):2937-60. Erratum in: Stat Med. 2017 Jun 30;36(14 ):2320. — View Citation

Manzur AY, Kuntzer T, Pike M, Swan A. Glucocorticoid corticosteroids for Duchenne muscular dystrophy. Cochrane Database Syst Rev. 2004;(2):CD003725. Review. Update in: Cochrane Database Syst Rev. 2008;(1):CD003725. — View Citation

Markham A, Bryson HM. Deflazacort. A review of its pharmacological properties and therapeutic efficacy. Drugs. 1995 Aug;50(2):317-33. Review. — View Citation

Markham LW, Spicer RL, Khoury PR, Wong BL, Mathews KD, Cripe LH. Steroid therapy and cardiac function in Duchenne muscular dystrophy. Pediatr Cardiol. 2005 Nov-Dec;26(6):768-71. — View Citation

Mayhew A, Cano S, Scott E, Eagle M, Bushby K, Muntoni F; North Star Clinical Network for Paediatric Neuromuscular Disease. Moving towards meaningful measurement: Rasch analysis of the North Star Ambulatory Assessment in Duchenne muscular dystrophy. Dev Med Child Neurol. 2011 Jun;53(6):535-42. doi: 10.1111/j.1469-8749.2011.03939.x. Epub 2011 Mar 17. — View Citation

Mendell JR, Moxley RT, Griggs RC, Brooke MH, Fenichel GM, Miller JP, King W, Signore L, Pandya S, Florence J, et al. Randomized, double-blind six-month trial of prednisone in Duchenne's muscular dystrophy. N Engl J Med. 1989 Jun 15;320(24):1592-7. — View Citation

Merlini L, Cicognani A, Malaspina E, Gennari M, Gnudi S, Talim B, Franzoni E. Early prednisone treatment in Duchenne muscular dystrophy. Muscle Nerve. 2003 Feb;27(2):222-7. — View Citation

Moxley RT 3rd, Ashwal S, Pandya S, Connolly A, Florence J, Mathews K, Baumbach L, McDonald C, Sussman M, Wade C; Quality Standards Subcommittee of the American Academy of Neurology; Practice Committee of the Child Neurology Society. Practice parameter: corticosteroid treatment of Duchenne dystrophy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2005 Jan 11;64(1):13-20. — View Citation

O'Brien PC. Procedures for comparing samples with multiple endpoints. Biometrics. 1984 Dec;40(4):1079-87. — View Citation

Phillips MF, Quinlivan RC, Edwards RH, Calverley PM. Changes in spirometry over time as a prognostic marker in patients with Duchenne muscular dystrophy. Am J Respir Crit Care Med. 2001 Dec 15;164(12):2191-4. — View Citation

Pocock SJ, Geller NL, Tsiatis AA. The analysis of multiple endpoints in clinical trials. Biometrics. 1987 Sep;43(3):487-98. — View Citation

Quinlivan R, Roper H, Davie M, Shaw NJ, McDonagh J, Bushby K. Report of a Muscular Dystrophy Campaign funded workshop Birmingham, UK, January 16th 2004. Osteoporosis in Duchenne muscular dystrophy; its prevalence, treatment and prevention. Neuromuscul Disord. 2005 Jan;15(1):72-9. Epub 2004 Dec 10. — View Citation

Reitter B. Deflazacort vs. prednisone in Duchenne muscular dystrophy: trends of an ongoing study. Brain Dev. 1995;17 Suppl:39-43. — View Citation

Sansome A, Royston P, Dubowitz V. Steroids in Duchenne muscular dystrophy; pilot study of a new low-dosage schedule. Neuromuscul Disord. 1993 Sep-Nov;3(5-6):567-9. — View Citation

Silversides CK, Webb GD, Harris VA, Biggar DW. Effects of deflazacort on left ventricular function in patients with Duchenne muscular dystrophy. Am J Cardiol. 2003 Mar 15;91(6):769-72. — View Citation

Simonds AK, Muntoni F, Heather S, Fielding S. Impact of nasal ventilation on survival in hypercapnic Duchenne muscular dystrophy. Thorax. 1998 Nov;53(11):949-52. — View Citation

Stein RE, Jessop DJ. Functional status II(R). A measure of child health status. Med Care. 1990 Nov;28(11):1041-55. Erratum in: Med Care 1991 May;29(5):following 489. — View Citation

Tang DI, Geller NL, Pocock SJ. On the design and analysis of randomized clinical trials with multiple endpoints. Biometrics. 1993 Mar;49(1):23-30. — View Citation

Varni JW, Seid M, Knight TS, Uzark K, Szer IS. The PedsQL 4.0 Generic Core Scales: sensitivity, responsiveness, and impact on clinical decision-making. J Behav Med. 2002 Apr;25(2):175-93. — View Citation

Varni JW, Seid M, Kurtin PS. PedsQL 4.0: reliability and validity of the Pediatric Quality of Life Inventory version 4.0 generic core scales in healthy and patient populations. Med Care. 2001 Aug;39(8):800-12. — View Citation

Varni JW, Seid M, Rode CA. The PedsQL: measurement model for the pediatric quality of life inventory. Med Care. 1999 Feb;37(2):126-39. — View Citation

Witt WP, Kasper JD, Riley AW. Mental health services use among school-aged children with disabilities: the role of sociodemographics, functional limitations, family burdens, and care coordination. Health Serv Res. 2003 Dec;38(6 Pt 1):1441-66. — View Citation

Xie H, Heitjan DF. Sensitivity analysis of causal inference in a clinical trial subject to crossover. Clin Trials. 2004 Feb;1(1):21-30. Erratum in: Clin Trials. 2004;1(5):2 p following 474. Clin Trials. 2005;2(2):194. — View Citation

* Note: There are 56 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Forced Vital Capacity	Forced vital capacity was measured during a spirometry test. Forced expiratory volume (FEV) measures how much air a person can exhale during a forced breath. Forced vital capacity (FVC) is the total amount of air exhaled during the FEV test.	Average of Months 3, 6, 12, 18, 24, 30 and 36 visits
Primary	Rise From the Floor Velocity	Reciprocal of time to rise from the floor	Average of Months 3, 6, 12, 18, 24, 30 and 36 visits
Primary	Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction With Treatment Score	The TSQM Global Satisfaction with Treatment is a 14-item questionnaire that ranges from 0 - 100 with higher scores indicating better outcomes.	Average of Months 3, 6, 12, 18, 24, 30 and 36 visits
Secondary	North Star Ambulatory Assessment (NSAA) Score	The North Star Ambulatory Assessment (NSAA) is a 17-item rating scale that is used to measure functional motor abilities in ambulant children with Duchenne Muscular Dystrophy (DMD). It is usually used to monitor the progression of the disease and treatment effects.; The activities are graded as follows: 2 - "Normal" - no obvious modification of activity; 1 - Modified method but achieves goal independent of physical assistance from another 0 - Unable to achieve independently This scale is ordinal with 34 as the maximum score indicating fully-independent function.	Average of Months 3, 6, 12, 18, 24, 30 and 36 visits
Secondary	6 Minute Walk Test	Measures the total distance walked in 6 minutes averaged over all post-baseline follow-up visits through Month 36.	Average of Months 3, 6, 12, 18, 24, 30 and 36 visits
Secondary	Range of Motion (Goniometry) of Left Ankle	Range of motion at the ankle joint in dorsiflexion measured in degrees from plantigrade averaged over all post-baseline visits.	Average of Months 3, 6, 12, 18, 24, 30 and 36 visits
Secondary	Range of Motion (Goniometry) of Right Ankle	Range of motion at the ankle joint in dorsiflexion measured in degrees from plantigrade averaged over all post-baseline visits.	Average of Months 3, 6, 12, 18, 24, 30 and 36 visits
Secondary	Number of Participants Who Tolerated the Regimen	The number of participants who completed 36 months of follow-up on the originally assigned dosage (for weight) of study medication.	3 years
Secondary	Heart Rate	Measured by trans-thoracic echocardiogram and 12-lead ECG.	36 months
Secondary	Quality of Life - Parent	Quality of life was measured by parent/guardian self-report for all children utilizing the PEDSQL measurement tool. This is a 23-question tool. Scores can range from 0 to 100, with higher scores indicating better quality of life for the child.	Average of Months 12, 24, and 36 visits
Secondary	Quality of Life- Child	Quality of life was measured by child self-report in children age 5 and older utilizing the PEDSQL measurement tool. This is a 23-question tool. Scores can range from 0 to 100, with higher scores indicating better quality of life.	Average of Months 12, 24, and 36 visits
Secondary	Left Ventricular Ejection Fraction Percent	Measured by trans-thoracic echocardiogram and 12-lead ECG.	36 months
Secondary	Fractional Shortening Percent	Measured by trans-thoracic echocardiogram and 12-lead ECG.	36 months
Secondary	PR Interval	Measured by trans-thoracic echocardiogram and 12-lead ECG.	36 months
Secondary	Participant Weight		36 months
Secondary	Participant Height		36 months
Secondary	Participant Body Mass Index		36 months