Priapism In Sickle Cell Study
PISCES
“promoting men’s health”
Dr Ade Olujohungbe
Consultant Haematologist & Hon Lecturer
University Hospital Aintree NHS Trust
Lower Lane
Liverpool
PI
SC ES L9 7AL
Priapism in Sickle Cell
Disease (SCD)
Priapus; Greek God of fertility
Painful, persistent, purposeless,
penile erection first described by
Tripe in 1845
First associated with Sickle cell
anaemia in 1934 (Diggs)
Precise characteristics in SCD
poorly documented
PI
SC ES
Causes of Priapism
Idiopathic
Sickle cell disease
Other haematologic diseases e.g. CGL
Chronic renal failure/ dialysis
Oral medications e.g. Antihypertensives
Intracavernous injection
Perineal trauma
Neoplastic infiltration
Miscellaneous e.g. recreational drugs
Detumescence
Thought to be an active
process brought about by a-
agonist mediated contraction
of venous sinusoids in
corpora cavernosa
Smooth muscle relaxation
with dilation of arteries -
increased flow
Compression of sub-tunical
venous plexuses - reduced
outflow
Genetic polymorphisms associated with
Priapism in SCD
Gene Gene function Chromosome
location
TGFBR type 3 TGFb superfamily 1p33
(anti inflammatory)
Aquaporin Transporter and ion 7p14
channels
Integrin av Adhesion 2q31
A1 subunit of Coagulation 6p25
coagulation factor
XIII
Klotho NO biology 13q12
Patho-physiology & Clinical features of
priapism in SCA
Poorly understood - ? Triggered by relative hypoxia
leading to sickling and venous stasis Cavernosography
has demonstrated deep dorsal vein occlusion
Low flow type: Painful, Cavernous blood hypoxic in
established priapism (PaO2 400
Patients on exchange transfusion programme
Flow Through Study
PI
SC ES
Self Help strategies
Vigorous Hydration
Simple or Compound analgesia
Mild –moderate exercise.
Warm baths
Voiding urine
A minimum observation period of 3 months is important to establish
event rate before phase B
Sympathomimetic amine
a and b adrenergic
actions.
Off counter preparation
Priapism In Sickle Cell Study
Etilifrine hydrochloride
Unlicensed in the UK
Available in Argentina, Austria, Belgium,
Brazil,Chile, Finland, France, Germany, Greece,
Italy, Mexico, Norway,Portugal, S.Africa, Spain,
Sweden, Switzerland and Thailand
Trade names Effortil, Eti-puren, Thomasin etc.
Licensed for hypotension
Designated an orphan drug in EU for use in
priapism
“Spot The Diagnosis”
Phase A
PISCES Study
Phase A
Patient ID ………..
Centre ID ………..
Phase B
PISCES Study
Phase B
Patient ID ………..
Centre ID ………..
End of Study
Patients will discuss subsequent therapy
with their PI’s ( based on study or mutual
consent).
Analysis of the study on completion
Results fed back to PI’s and patient
groups through meetings, publications
and newsletter.
Serious Adverse Events (SAE’s)
An undesirable experience occurring to a patient
whether or not considered related to investigational
drug which results in
Death
Immediate risk of death at time of observation
Hospitalisation or prolongation of hospital stay
Persistent or significant disability.
A congenital anomaly or birth defect
SAE’s must be reported within 24hrs of first full
working day or after weekend to Statistician or Chief
Investigator by fax/email.
Role and Responsibilities
Trial Steering group Responsible for day to day
(Independent chair) running of trial.
Mr. Nick George, Consultant Urologist & Provide advice to PI’s.
Senior Lecturer, South Manchester
University Teaching Hospital
University Hospital, Aintree
Trial sponsor
Independent data Monitoring Access to unblinded data.
Committee. Monitor data and make
recommendations to TSG.
Can stop study.
Principal Investigator (PI). Overall responsibility for patient
and conduct of trial according to
GCP in centre.
Actively recruit patients from
centre.
P I SC ES
MRC guidelines for good clinical practice 1998
Communication (Newsletter)
Trial Website (forms)
www.anaemiaweb.org.pisces.htm
Peter wondered
why his floppy disk
was malfunctioning
??
??