Clinical trial NCT04420585
Conditions: Nocturnal Enuresis Anemia, Sickle Cell
Sponsor: Montefiore Medical Center
Start date: 2020-07-07; Completion date: 2023-06-12
Enrollment: 8 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study assesses if using the medication desmopressin will decrease nightime bedwetting in children with sickle cell disease.

Detailed description:
Night time bedwetting is a common complication of sickle cell disease, and affects up to 30 % of children. Desmopressin is an oral medication that increases water reabsorption in the kidneys. Studies have shown that it is effective in decreasing bedwetting episodes in children without sickle cell disease. Chronic sickling episodes causing damage to the kidneys could cause permanent damage and may make this treatment ineffective in sickle cell disease. This trial will inform pediatric sickle cell doctors if desmopressin is an appropriate treatment for bed wetting in the investigators patients.

This study expanded upon a previously terminated study which had separately registered (NCT02636387, ID: 2014-3768).

Arms: arm 1: Desmopressin 0.2mg tablets, dose titrated to effect
Interventions: intervention 1: Desmopressin
Intervention descriptions: intervention 1: Two desmopressin 0.2 mg tablets at bedtime for 14 days and monitoring if \<50 % improvement

Protocol documents:
Prot_SAP_000.pdf: 
1
Principal Investigator: Kerry Morrone, M.D.  
Desmopressin as a therapy for nocturnal enuresis in patients with Sickle Cell Disease
January 20, 2020
Background:
Nocturnal enuresis is more prevalent in patients with sickle cell disease (SCD) than the general 
pediatric population. The International Children’s Continence Society (ICCS) defines enuresis as 
discrete episodes of urinary incontinence during sleep in children ≥5 years of age.1 The rate of 
nocturnal enuresis in patients with sickle cell disease (Hemoglobin SS, SB0thal and SB+thal)  
ranges from  28%2 to 52%3 of boys and 11%2 -38%3 of girls, compared to 7% of boys and 3% of 
girls at age 5 in the general population.2  Enuresis becomes less common with age, in one study 
decreasing from 36% in patients between 8-10 years to 9% of patients aged 18-20 years4. 
Nocturnal enuresis has been shown to affect patient’s quality of life5, and can lead to social and 
emotional stigma, stress and inconvenience. Currently, there is no mainstay of therapy for 
nocturnal enuresis in patients with SCD. In the general pediatric population, several therapies are 
used to manage nocturnal enuresis, including behavior modification, alarms and 
pharmacotherapy such as desmopressin and less often, imipramine. Desmopressin is a synthetic 
analogue of arginine vasopressin which exerts an antidiuretic effect by increasing water 
reabsorption in the distal tubules and collecting ducts of the kidneys. In the general pediatric 
population, bed-wetting was reduced by 1.34 nights per week (95% CI 1.11-1.57) in patients 
who received desmopressin compared to those who received placebo. Patients receiving 
desmopressin were almost twice as likely to achieve at least 14 consecutive dry nights compared 
to placebo6.  
Desmopressin is not systematically prescribed to patients with SCD who have nocturnal 
enuresis. This may be due to the thought that these patients have an irreversible and progressive 
defect in the renal medulla secondary to chronic sickling episodes, and desmopressin may be 
ineffective, as this defect is not related to the signaling pathways in which desmopressin acts. 
This also may be due to lack of adequately powered clinical trials demonstrating efficacy. More 
likely, patients with SCD have many medical complications associated with their disease and 
symptoms of seemingly lesser conditions such as nocturnal enuresis may be minimized or 
ignored. 
1  Nevéus, T., et al., The standardization of terminology of lower urinary tract function in children and adolescents: 
report from the Standardization Committee of the International Children's Continence Society. The Journal of 
Urology, 2006. 176(1): 314-324. 
2 Barakat, LP., et al., Nocturnal Enuresis in Pediatric Sickle Cell Disease. Journal of Developmental and Behavioral 
Pediatrics, 2001. 22(5): p. 300-305
3 Readett, D R J., et al., Nocturnal enuresis in sickle cell haemoglobinopathies. Archives of Disease in Childhood, 
1990. 65: 290-293
4 DeBaun, M R., et al., Enuresis Is a Common and Persistent Problem Among Children and Young Adults with Sickle 
Cell Anemia. Urology, 2008. 72(1):81-84
5 Naitoh, Y., et al., Health Related Quality of Life for Monosymptomatic Enuretic Patients and Their Mothers. The 
Journal of Urology, 2012. 188(5): 1910-1914
6 Glazener CMA, Evans JHC. Desmopressin for nocturnal enuresis in children. Cochrane Database of Systematic 
Reviews, 2002, Issue 3. Art. No.: CD002112. DOI: 10.1002/14651858.CD002112 
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The mechanism underlying the higher prevalence of enuresis in patients with sickle cell 
disease is not completely understood. Several hypotheses have been studied and the etiology is 
thought to be multifactorial.  The predominant theory proposes that enuresis occurs secondary to 
a defect in the concentrating capability of the kidney caused by the sickling of red blood cells in 
the hypertonic, acidic and hypoxic renal medulla. Sickling leads to occlusion of the vasa recta 
and impairment of blood flow.7 This interferes with the countercurrent mechanism of the kidney, 
and impedes free water reabsorption leading to increased urinary volume, hyposthenuria and 
oftentimes delayed attainment of nocturnal urinary continence. 
Several studies support this theory by demonstrating decreased urine osmolality in 
patients with sickle cell disease compared to healthy controls. Statius Van Eps et al, 
demonstrated that patients with Hemoglobin SS disease have decreased urine osmolality at a 
young age compared to patients with Hemoglobin SC, AS and AA, with a progressive decline 
over time until a plateau at approximately age ten.8 Noll et al compared patients with sickle cell 
disease to sibling controls to demonstrate higher rates of enuresis and nocturia in patients with 
SCD correlating with decreased urine specific gravity measurements.9  Readett et al challenged 
this hypothesis by comparing urine osmolality of enuretic patients with SCD to non-enuretic 
patients with SCD, demonstrating no significant difference in the urine osmolality after a water 
deprivation test between the two groups.  Their study showed that enuretic patients had a lower 
maximum functional bladder capacity and higher overnight urine volume to bladder capacity 
ratio compared to controls, suggesting that these factors may contribute to enuresis in patients 
with sickle cell disease.10 The study also collected subjective data from families who assessed 
patients with nocturnal enuresis as deep sleepers. In another study, Readett et al noted a 
correlation between large family size and likelihood of enuresis in boys3, further suggesting a 
social and environmental component to enuresis.  
Few studies have been done to evaluate the efficacy of standard therapies for nocturnal 
enuresis in patients with SCD. One study by Figueroa et al11 supports the use of desmopressin in 
patients with SCD. This study examined a population of 91 patients with sickle cell disease age 
6-21 with a 29.6% prevalence of nocturnal enuresis. The researchers looked at the effect of 
enuresis alarms and intranasal desmopressin on the rate of nocturnal enuresis. Ten patients 
elected to receive desmopressin, with four showing complete resolution of symptoms, and two 
showing greater than 50% improvement of symptoms while receiving medication, an overall 
60% rate of improvement.  Two patients elected to use enuresis alarms with no improvement in 
symptoms after three and four months respectively. While this study showed the desmopressin 
may be effective in this population, it was limited by its small sample size and lack of 
randomization or blinding. This study also used intranasal desmopressin, which is not routinely 
7 Becker, A, Sickle cell nephropathy : challenging the conventional wisdom, Pediatric Nephrology, 2011. 26: 2099-
2109
8 Statius Van Eps, LW., et al,. The relation between age and renal concentrating capacity in sickle cell disease and 
hemoglobin C disease. Clinica Chimia Acta, 1970. 27: 501-511
9 Noll, JB,. et al., Enuresis and Nocturia in Sickle Cell Disease. The Journal of Pediatrics, 1967. 70: 965-967
10 Readett, D R J., et al., Determinants of Nocturnal Enuresis in Homozygous Sickle Cell Disease. Archives of Disease 
in Childhood, 1990. 65:615-618
11 Figueroa, E,. et al., Enuresis in Sickle cell Disease. The Journal of Urology, 1995. 153: 1987-1989
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used as it is associated with variable absorption patterns and thus increased side effects compared 
to the oral preparation, including the serious side effect of hyponatremia6. 
A survey conducted from July to September 2010 at the CHAM Hematology clinic, where we 
follow over 600 sickle cell patients, showed that of 63 patients between the ages of 5-21, 27% 
reported nocturnal enuresis.  Table 1 shows rates of nocturnal enuresis by age group in this 
population. This data is consistent with the increased rate of nocturnal enuresis previously 
reported, suggesting that we will have a more than an adequate number of patients eligible to 
participate in this study.
Table 1
Age
Enuretic
Non Enuretic
% Enuretic
5-10
8
28
22.2%
 11-21
9
18
33.3%
Total
17
46
27 %
Our initial objective was to conduct a randomized placebo controlled double blinded study to 
assess the efficacy of desmopressin on the rate of nocturnal enuresis in patients with SCD 
compared to placebo. We also planned to utilize quality of life and fatigue scale questionnaires to 
evaluate the quality of life in these patients prior to and after treatment.  We hypothesized that 
patients receiving desmopressin would demonstrate fewer episodes of nocturnal enuresis 
compared to those receiving placebo. Due to low accrual with the study (five participants 
completed the study and nine participants withdrew from the study), and due to the fact that 
DDAVP treatment for nocturnal enuresis is already standard of care in a general pediatric 
population, it was determined beneficial by the investigators to prescribe DDAVP as standard of 
care and to eliminate the placebo group. The study team will prospectively collect quality of life 
data for the patients prior to prescribing DDAVP and then one month after initiating treatment 
with DDAVP. Prior to starting DDAVP an eligibility diary would be filled out on recollection by 
patient on their enuresis patterns for the past 2 weeks (Appendix 1A). Enuresis diaries would be 
given to patients and families to track their enuresis but also could be filled out retrospectively 
with study coordinator either in person or over the phone. We propose to then analyze their 
laboratory, physical exam, imaging, data prospectively for those patients administered DDAVP 
as part of their clinical care upon starting the DDAVP. We would prospectively administer 
surveys on willing participants prior to starting DDAVP and then one month into the 
intervention.  To provide information to the sickle cell research community we propose the 
following interventions. 
The primary objective of this study is:
1. To prospectively assess if the use of desmopressin in patients with sickle cell disease and 
nocturnal enuresis will decrease the number of nighttime episodes of enuresis by 50% 
after initiating DDAVP at 0.4 mg nightly dose with dose escalation as clinically 
appropriate.  
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Secondary objectives are:
1. To determine if patients with sickle cell disease and nocturnal enuresis receiving 
desmopressin will have an improved quality of life compared to their baseline.  
2. To determine if patients with sickle cell disease and nocturnal enuresis receiving 
desmopressin will have less daytime fatigue compared to their baseline data. 
3. To determine if the use of desmopressin in patients with nocturnal enuresis improves 
rates of nocturia, defined as episodes of nighttime awakening to void in children ≥5 years 
of age12, compared to prior to initiating treatment with DDAVP. 
Study Site: 
This study will be implemented at the Children’s Hospital at Montefiore (CHAM). 
Patients with sickle cell disease will be recruited from the Hematology outpatient clinic and 
inpatient unit.  
Population:
Inclusion Criteria:
1. Patients with Hemoglobin SS, SC, SB0thal or SB+thal
2. Patients age 8-21
3. Patients with at least two episodes of primary nocturnal enuresis per week or four 
episodes over the two weeks prior to enrollment. 
4. Patients with secondary enuresis who have been evaluated and cleared by a pediatric 
urologist as not having other etiologies of enuresis (e.g. overactive detrusor activity, a 
genitourinary anatomic abnormality) 
Exclusion Criteria:
1. Patients with developmental delay or neurologic dysfunction secondary to stroke
2. Patients with hypertension or underlying renal disease. 
3. Patients with genitourinary anatomic abnormalities.  Any prior renal ultrasound showing 
normal genitourinary anatomy is sufficient to clear a patient for the study. 
4. Patients with daytime urinary incontinence 
5. Patients with glucosuria on urinalysis. 
6. Patients with secondary nocturnal enuresis who have not been evaluated by a pediatric 
urologist to rule out other etiologies of enuresis. 
7. Patients who are pregnant. 
8. Patients receiving another medicine for nocturnal enuresis (e.g. imipramine).
9. Patients aged 8-17 who are experiencing pain. 
12  Nevéus T et al, The standardization of terminology of lower urinary tract function in children and adolescents: 
report from the Standardisation Committee of the International Children's Continence Society. J Urol. 
2006;176(1):314. Of note, the term nocturia does not apply to children who awaken for reasons other than a need 
to void.
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Methods: 
Subjects: 
Patients will be recruited for the study in the CHAM outpatient hematology clinic and the 
inpatient Hematology unit. Medical staff will be educated about the study and designated 
individuals will obtain consent for administering the PROMIS Fatigue survey prior to initiating 
medication. 
Enrollment: 
This study will be a cohort analysis of a standard of care medication administered for nocturnal 
enuresis. Prior to starting this standard of care medication patients will fill out the PROMIS 
questionnaire on fatigue. Patients with sickle cell disease who fit the inclusion criteria will be 
notified about the study when they are seen in hematology clinic, prior to discharge from 
hospitalization or via phone by study staff. Patients enrolled during hospitalization will not start 
the trial until a post-hospitalization follow up visit.  At this point, the study will be introduced 
and discussed. Written consent for the survey will be obtained from interested and eligible 
guardians, or patients, if they are older than 18 years old or an emancipated minor. Patients 7-17 
years of age will sign assent. Patients will also be identified for eligibility via the electronic 
medical record.  Patients who fit the inclusion criteria will be called and informed of the 
medication following a detailed script (see Appendix 6).  If they are interested, consent will be 
obtained at the next outpatient or inpatient visit. Patients and/or guardians will have the option to 
decline participation or opt out of the study at any point.
Intervention
Patients if they meet eligibility criteria will be prescribed DDAVP starting at 0.4 mg every night. 
Baseline data will be obtained from all patients enrolled in the study using data from 6 months 
prior to initiating DDAVP. This includes medical history specific to SCD, general medical 
history (see Appendix 2A), baseline data and labs within the last 6 months (Appendix 2B-D). 
Renal sonogram will be obtained to assess baseline degree of fibrosis, unless patient has previous 
normal renal sonogram as part of standard of care. 
The day that DDAVP is initiated, patients will complete the Promis Fatigue Scale to 
measure fatigue as a quality of life measure.  We will repeat this questionnaire in a month after 
starting DDAVP.
 Patients will receive 0.4 mg oral desmopressin tablet to be taken at bedtime and will 
receive similar instructions to take tablet at bedtime with minimal water. They will also be 
advised not to drink caffeinated beverages four hours before bedtime, not to drink any liquids 
after taking tablet, and to void right before bedtime. Patients will also be advised to discontinue 
medication if they develop symptoms of headache, nausea or vomiting, develop an acute illness, 
or if they are admitted to the hospital and are receiving intravenous fluids. 
Monitoring
Patients will be asked to keep an “enuresis diary” for four weeks (See Appendix 1B).  In the 
diary, patients will record their adherence to the medication, if they had an episode of enuresis, 
as well as the number of nighttime awakenings specifically secondary to nocturia (and not for 
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any other reason such as pain or anxiety). All patients will have a follow up call two weeks and 
four weeks after starting the medication by the study coordinator. Patients will be assessed for 
improvement in symptoms, medication adherence, and any side effects they are experiencing. 
Blood pressure, Chem-10, Urine and serum electrolytes and osmolality and urine analysis will be 
obtained if patient describes any adverse clinical symptoms as would be performed as part of 
standard of care.  Enuresis diaries will be reviewed, and if patients do not have at least a 50% 
improvement in symptoms they will be advised to make an appointment to investigate if 
adjustment of the medication based on clinical care would be appropriate. See Appendix 3 for a 
complete study timeline. 
Any patient that has a dose dependent side effect to the medication will have the dose 
reduced promptly and appropriate clinical management and follow up. If a patient has an acute 
VOC while taking study medication and is on intravenous fluids, the medicine will be held 
during the acute event. Individuals will be asked at the end of the study if they had a pain crisis 
or acute chest syndrome during this intervention.
Be advised that the patients will have up to one year to complete the study.  Although the 
study should only take 4 weeks the patient will not be removed from study unless their 
participation lasts longer than one year.  Children with sickle cell disease frequently have 
admissions related to their chronic disease that may prevent them from completing study within 
the 4 week time period. The medication works immediately and a stop in the medication will not 
cause a decrease in effect of the previous or current doses.  
Study tools: 
Promis Fatigue scale- PROMIS® instruments use modern measurement theory to assess patient–
reported health status for physical, mental, and social well–being to reliably and validly measure 
patient–reported outcomes (PROs) for clinical research and practice 13,14. PROMIS instruments 
measure concepts such as pain, fatigue, physical function, depression, anxiety and social 
function. The Fatigue scale utilizes a 7–day recall period (items include the phrase "the past 7 
days") with five responses. The responses span from never (0) to almost always (4).  The Fatigue 
scale is a 10 item questionnaire whose scores can be approximated if a participant skips a 
question. A 10-item short form can be scored as long as the participant answered at least 5 items.  
The Pediatric PROMIS Fatigue scale has been validated for patients aged 8-17 years of age.  The 
surveys will be administered at initiation of medication (week 1) and after completion of 4 weeks 
of medication. If patients stop and restart the medication the survey will be taken after 4 
consecutive weeks of at least 50 % compliance with the medication.   This will assess differences 
in the patients’ perception of fatigue after starting the medication. Please see Appendix 4 for 
Promis Fatigue Scale.
Statistics: 
For our study, success in treatment will be defined as a 50% reduction in bedwetting episodes. 
Our primary endpoint is the improvement in number of wet nights (binary outcome variable) 
comparing pretreatment and post treatment use of desmopressin. We can expect little or no 
change in untreated subjects and therefore presume that maximum 10% will improve on their 
own. Based on the study by Figueroa et al,11 we can presume that 60% of patients will improve 
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with desmopressin treatment. In order to detect this 50% difference, we will enroll 50 patients 
for the study so that the 95% CI for proportion of subjects with improvement after treatment is 
expected to be (0.46, 0.74) thus will be able to exclude 10% that is expected for untreated 
subjects.  In a secondary analysis, the improvement status will also be correlated to patient 
characteristics using a logistic regression model. Secondary endpoints are not powered
13 Magasi, S. et al. (2011). Content validity of patient reported outcomes: Perspectives from a 
PROMIS meeting. Quality of Life Research, 25 Aug 2011.
14Garcia, S. F. et al.  (2007). Standardizing patient–reported outcomes assessment in cancer 
clinical trials: a PROMIS initiative. Journal of Clinical Oncology, 25(32), 5106–12. 
Risks/Assessment of Safety and Mitigation of Risks
The overall incidence of adverse events with the use of desmopressin in patients with nocturnal 
enuresis is low. Reported adverse events are described as mild and transient, including headache, 
abdominal pain, nausea and dyspepsia. Adverse events report in patients treated with the 
intranasal formulations also included nasal congestion, rhinitis and epistaxis. The most serious, 
but uncommon adverse event is hyponatremia, which can induce seizures. This is reported more 
commonly with the intranasal formulation, but has also been noted with the tablet form.13 
Robson et al looked at published data via Medline from December 1972 to August 2006 and 
post-marketing safety data from December 1972-June 2005 to assess the safety of desmopressin 
with a focus on the safety of the oral formulation. They identified 21 clinical trials on 
desmopressin use in children with nocturnal enuresis, in which there were no reports of 
hyponatremia. 21 publications were identified that included 48 case reports of hyponatremia, all 
of which were associated with intranasal desmopressin use. Post-marketing safety data reports 
identified 151 cases of hyponatremia in patients with nocturnal enuresis, 145 of whom were 
treated with the intranasal formulation and 6 of whom received the desmopressin tablet. Based 
on their review, Robson et al identified several preventable risk factors for hyponatremia, 
including avoiding high fluid intake, prescribing higher than recommended dose of medication, 
use of medication in patients younger than six years, and concomitant administration of another 
medication for nocturnal enuresis. They also recommend immediate discontinuing use of 
medication if patient develops symptoms of headache, nausea or vomiting, or if they develop an 
acute intercurrent illness, or are hospitalized and receiving IV fluids. Desmopressin package 
insert from Ferring Pharmaceuticals also recommends fluid restriction and recommend use with 
caution in patients with habitual or psychogenic polydipsia who may be more likely to drink 
excessive amounts of water, putting them at greater risk of hyponatremia14.
In order to minimize the risk of an adverse event, patients will be given clear directions 
not to drink fluids after taking tablet. Patients will be advised to discontinue medication if they 
15Robson, W.L.M., et al., The Comparative Safety of Oral Versus Intranasal Desmopressin for the Treatment of 
Patients with Nocturnal Enuresis. The Journal of Urology, 2007. 178 (1): 24-30
16 Desmopressin Acetate Package Insert 
http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/pediatricadvisorycommittee/u
cm215090.pdf
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develop symptoms of headache, nausea or vomiting and contact their doctor immediately. Doses 
used in the study are within the recommended range of 0.2-0.6 mg. Patients receiving another 
medicine for nocturnal enuresis (e.g. imipramine) will not be included in the study. Side effects 
of the medication will be monitored at each follow up visit. 
Refusal to participate in the study including answering surveys will have no effect on the care 
that the child or the parent/caregiver receives. If the patient wants to be prescribed DDAVP and 
not complete the rest of the study (diaries, surveys), since this is standard of care medication it 
will still be prescribed and monitored as clinically indicated. 
Potential Benefits:
There is the potential to benefit directly from improvement of their enuresis and with that 
potentially improved quality of sleep and hydration status, both of which may are key factors in 
mitigating vaso-occlusive crises. 
Data Safety Monitoring Plan
Data Quality
Data quality will be monitored by the investigators and DSMC.  The following elements will be 
monitored:  recruitment proceeding as expected; study subjects match the inclusion/exclusion 
criteria; deviations from the protocol; adverse events; accuracy and confidentiality of all 
information both in the case report forms and electronic databases.  DSMC will meet after the 
first 20 patients are enrolled to assess the quality of the data.
Safety Monitoring 
Safety monitoring will be conducted by the investigators and DMSC.  All adverse events will be 
indicated on the source documentation for the study, and on the specific adverse event case 
report form.  The following information about adverse events will be collected:  1) the onset and 
duration; 2) severity or intensity; 3) relationship to study drug; 4) action taken 5) outcome.  The 
investigators will determine the severity of the event, assign attribution to event, and monitor the 
event until its resolution.  For the purpose of this trial, the following conditions are expected due 
to the subject’s underlying disease process or treatment and are not regarded as serious adverse 
events.  
Expected AE due to sickle 
cell disease
Expected AE due to sickle 
cell disease
Expected AEs 
due to IVIG
Expected AE due 
to narcotic usage
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Acute chest syndrome
Hyperplastic bone marrow
Asthenia
Constipation
Anemia
Hypoxemia (pO2 < 65 mm 
Hg)
Back pain
Hives
Aplastic crisis/anemia
Infection, encapsulated 
organism
Fever/Chills
Pruritus
Arthralgia
Jaundice
Cough
Respiratory 
depression
Avascular Necrosis of 
hip/shoulder
Leukocytosis
Headache
Urinary retention
Bone infarction
Meningitis
Hypertension
Nausea/vomiting
Cardiomegaly
Nausea and vomiting
Pharyngitis
Cholecystitis
Pain, joints or long bones
Rash
Cranial nerve palsy
Pain abdominal, chest, or 
back
Urticaria
Decreased lung function
Priapism
Pruritis
Delayed growth/puberty
Pulmonary hypertension
Dizziness
Depressed ESR
Pulmonary infiltrates on 
CXR
Back pain 
Elevated serum bilirubin
Pyelonephritis
Arthralgia
Elevated urinary urobilinogen
Renal papillary necrosis
Nausea/vomiting
Fever
Reticulocytosis
Diarrhea
Hand-foot syndrome
Retinal disease
Hematuria
Retinal hemorrhage
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Adverse events (Grade 3-5 severity in the CTCAE of the latest version) will be actively tracked 
in real time on each patient. 
Trial will be put on hold if any of the following criteria are met: 
The trial will be put on hold (with no further subject enrollment and treatment) pending IRB and 
DSMC review if: 
1) Cumulatively 2 patients experience an unexpected possibly related Grade 3 serious adverse 
event, or 
2) 1 patient experiences an unexpected possibly related Grade 4-5 serious adverse event, or 
3) 1 patient experiences an unexpected possibly related seizure episode of Grade 3 severity or 
higher. 
The determination of whether the adverse event is definitely related to DDAVP or not will be 
made by the IRB, and DSMC and accordingly a decision to stop the trial completely or proceed 
will be made by both agencies. No study enrollment or treatment will occur while the triggering 
event is being reviewed.
Data Safety and Monitoring Board
Data quality will be monitored by an independent 3-person DSMC board appointed from within 
the institution to ensure safe and effective conduct of the trial and recommend conclusion of the 
trial if significant risks have developed or the trial is unlikely to be concluded successfully.  The 
board members are i) a pediatric hematologist/oncologist knowledgeable in sickle cell disease 
not involved in the trial (Dr. Alexander Chou); ii) Dr. Michael Rinke, a pediatric hospitalist who 
is a quality expert and with knowledgeable in statistics and study design iii) Dr. Kimberly Reidy, 
a pediatric nephrologist and iv) Dr. Xiaonan Xue, a statistician in the department of 
epidemiology and population health. Dr. Alexander Chou will be the executive secretary of the 
Hepatic sequestration
Rhabdomyolysis
Hemolysis
Sepsis
Hepatosplenomegaly
Skin ulcers
Hyposthenuria
Splenic sequestration
IRB NUMBER: 2020-11268
IRB APPROVAL DATE: 07/07/2020
IRB NUMBER: 2020-11268
IRB APPROVAL DATE: 07/07/2020
IRB NUMBER: 2020-11268
IRB APPROVAL DATE: 07/07/2020
IRB NUMBER: 2020-11268
IRB APPROVAL DATE: 07/07/2020


11
DSMC.  The DSMC will meet with the Principal Investigator after the first 20 patients have 
completed the trial and then at the end of the trial and perform the following activities:
a.
Assess participant safety, including:
i.  All protocol deviations and adverse events
ii.  All scientific or therapeutic developments that may have an impact on the safety of the 
participants or the ethics of the study.
iii.  Benefit/risk ratio of procedures and participant burden
b. Evaluate trial progress, including:
i. Quality, accuracy, and timeliness of collected data and statistical analysis
ii. Selection, recruitment, and retention of participants
iii. Confidentiality of trial data
iv. Efficacy of the study intervention
c.
Performance of clinical research sites, including:
i. Performance of clinical research pharmacy and the core lab
ii. Adherence to protocol requirements
d. Make recommendations to the IRB and investigators, including:
i. Continuation or conclusion of the trial
ii. Amendments to the study protocol and consent forms
Protection of Privacy:
Patient data will be confidential and only personnel directly involved in the study will have 
access to it. All patient data will be coded and entered into a password protected electronic 
database.
IRB NUMBER: 2020-11268
IRB APPROVAL DATE: 07/07/2020
IRB NUMBER: 2020-11268
IRB APPROVAL DATE: 07/07/2020
IRB NUMBER: 2020-11268
IRB APPROVAL DATE: 07/07/2020
IRB NUMBER: 2020-11268
IRB APPROVAL DATE: 07/07/2020