Transcranial Doppler (TCD) With Transfusions Changing to Hydroxyurea

Phase 3 Terminated 159 enrolled Children's Hospital Medical Center, Cincinnati Ann & Robert H Lurie Children's Hospital of Chicago · collab Baylor College of Medicine · collab Boston Children's Hospital · collab Children's Healthcare of Atlanta · collab Children's Hospital of Philadelphia · collab Children's Hospital of The King's Daughters · collab Children's Hospitals and Clinics of Minnesota · collab Children's National Research Institute · collab Columbia University · collab Duke University · collab East Carolina University · collab Medical University of South Carolina · collab National Heart, Lung, and Blood Institute (NHLBI) · collab Nemours Children's Clinic · collab St. Jude Children's Research Hospital · collab State University of New York - Downstate Medical Center · collab Steven and Alexandra Cohen Children's Medical Center · collab The Hospital for Sick Children · collab University Hospitals Cleveland Medical Center · collab University of Alabama at Birmingham · collab University of Miami · collab University of Mississippi Medical Center · collab University of South Alabama · collab University of Texas Southwestern Medical Center · collab Wayne State University · collab

RandomizedParallel-groupOpen-labelPrevention

Summary

The primary goal of the Phase III TWiTCH trial is to compare 24 months of alternative therapy (hydroxyurea) to standard therapy (transfusions) for pediatric subjects with sickle cell anemia and abnormally high (≥200 cm/sec) Transcranial Doppler (TCD) velocities, who currently receive chronic transfusions to reduce the risk of primary stroke. For the alternative treatment regimen (hydroxyurea) to be declared non-inferior to the standard treatment regimen (transfusions), after adjusting for baseline differences, the hydroxyurea-treated group must have a mean TCD velocity similar to that observed with transfusion prophylaxis.

Timeline

Start: 2011-08
Primary completion: 2015-03
Completion: 2015-11

Outcome

Met primary endpoint

Stopped: “The study was stopped early due to successfully meeting the primary endpoint”

paper At the first scheduled interim analysis, non-inferiority was shown and the sponsor terminated the study. PMID 26670617 ↗

paper Non-inferiority (p=8·82 × 10(-16)) and post-hoc superiority (p=0·023) were met. PMID 26670617 ↗

Publications

Ware RE, Davis BR, Schultz WH, Brown RC, Aygun B, Sarnaik S, Odame I, Fuh B, George A, Owen W, Luchtman-Jones L, Rogers ZR, Hilliard L, Gauger C, Piccone C, Lee MT, Kwiatkowski JL, Jackson S, Miller ST, Roberts C, Heeney MM, Kalfa TA, Nelson S, Imran H, Nottage K, Alvarez O, Rhodes M, Thompson AA, Rothman JA, Helton KJ, Roberts D, Coleman J, Bonner MJ, Kutlar A, Patel N, Wood J, Piller L, Wei P, Luden J, Mortier NA, Stuber SE, Luban NLC, Cohen AR, Pressel S, Adams RJ. Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia-TCD With Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial. Lancet. 2016 Feb 13;387(10019):661-670. doi: 10.1016/S0140-6736(15)01041-7. Epub 2015 Dec 6.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Hydroxyurea	Other / unclassified	100 mg/ml	Oral
Subject	Hydroxyurea	Other / unclassified	300 mg	Oral
Subject	Hydroxyurea	Other / unclassified	400 mg	Oral
Subject	Hydroxyurea	Other / unclassified	500 mg	Oral