A Phase 3 interventional study of Hydroxyurea and Placebo in Hematologic Diseases and Anemia, Sickle Cell, sponsored by National Heart, Lung, and Blood Institute (NHLBI). Completed at 14 sites in United States. Open to participants aged 9 Months to 18 Months. Per ClinicalTrials.gov, last updated 2020-08-19.
Sponsored by National Heart, Lung, and Blood Institute (NHLBI) · Phase 3, Interventional, and Prevention
The purpose of this study is to determine if hydroxyurea therapy is effective in the prevention of chronic end organ damage in pediatric patients with sickle cell anemia.
BACKGROUND:
In 1995, the Multicenter Study of Hydroxyurea (MSH) demonstrated that hydroxyurea is effective in decreasing the frequency of painful crises, hospitalizations for crises, acute chest syndrome, and blood transfusions by 50%. The recently completed phase II study of hydroxyurea in children (PED HUG) demonstrated that children have a response to hydroxyurea similar to that seen in adults in terms of increasing fetal hemoglobin levels and total hemoglobin, and decreasing complications associated with sickle cell anemia. In addition, this study demonstrated that the drug does not adversely affect growth and development between the ages of 5 and 15. A recently completed pilot study of hydroxyurea given to children between the ages of 6 months and 24 months demonstrated that the drug is tolerated well by small infant, and that the fetal hemoglobin switch can be forced to remain in the "on position" by hydroxyurea administration.
A Special Emphasis Panel (SEP) met on April 12, 1996 to review the results of the MSH trial and the progress to date of the PED HUG study. The SEP recommended that NHLBI undertake the BABY HUG trial.
DESIGN NARRATIVE:
BABY HUG is a randomized, double-blind, placebo-controlled study to determine if hydroxyurea can prevent the onset of chronic end organ damage in young children with sickle cell anemia. Approximately 200 children with sickle cell disease will be recruited to receive either hydroxyurea or placebo. The children will be screened at study entry for signs of abnormal brain, kidney, pulmonary, and splenic function, and developmental milestones. They will then be randomly assigned to receive either hydroxyurea or placebo and followed yearly to assess chronic end organ damage of the major organ systems. The primary endpoint will be a 50% reduction in rates of damage to the major organs with surrogate markers of organ function during follow-up in Phase II of the trial.
1,733 studies on the registry are indexed under Anemia; 246 are open to participants now.
This study's enrollment of 193 is above the median of 94 across 1,291 interventional studies indexed under Anemia.
Browse Anemia studies →National Heart, Lung, and Blood Institute (NHLBI) is the lead sponsor of 1,117 studies on the registry; 71 are open to participants now.
Of its 57 completed or terminated interventional studies of FDA-regulated products, 49 (86%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
The following exclusion criteria are transient; patients can be re-evaluated for eligibility:
Participants will receive hydroxyurea.
Drug: Hydroxyurea
Participants will receive placebo.
Drug: Placebo
Participants will receive hydroxyurea.
Participants will receive placebo.
Treatment Differences of the Change in Qualitative Splenic Function From Baseline
Primary Endpoint: Spleen function was assessed by uptake of 99mTc sulfur colloid on liver-spleen scan before initiation of treatment (baseline) and 2 years later (exit). The results of each of the two scans were categorized as normal, functional but abnormal, or not functional by a panel of nuclear medicine specialists blinded to treatment assignment. The proportion of patients whose paired scans demonstrated a decline in splenic function was compared in the hydroxyurea versus placebo groups. The change in splenic function from baseline to 2 years was defined as worse if it changed from normal to decreased or absent, or decreased to absent; and not worse if it changed from decreased to decreased, normal to normal, or decreased to normal.
Time frame: Before initiation of treatment and at 2 years
Change From Baseline in the Renal Function That Was Measured by Diethylenetriaminepentaacetic Acid (DTPA) Glomerular Filtration Rate (GFR)
DTPA GFR was originally a co-primary efficacy outcome for the study. Later in May 29, 2009, this measurement was discontinued because of statistical futility (an extremely small chance that the difference between treatment groups would be statistically significant for this outcome) and the small risk posed by the radiation exposure involved with performing the DTPA GFR test. Subjects who had missing data at baseline or 2 years measurement were excluded from the analysis (29 subjects from the hydroxurea, and 31 subjects from the placebo group excluded).
Time frame: Before initiation of treatment and at 2 years
Change From Baseline in the Renal Function That Was Measured by Glomerular Filtration Rate (GFR) (Calculated Using Schwartz Formula)
Schwartz formula used to calculate GFR is: 0.55× height (cm)/serum creatinine (mg/dL). Where height is in cm and serum creatinine is in mg/dL. Children with missing baseline or 2 years GFR were excluded from the analysis.
Time frame: Before initiation of treatment and at 2 years
Change From Baseline in the Renal Function That Was Measured by GFR (Calculated Using New Schwartz Formula)
GFR was calculated using new Schwartz formula: 39.1× \[height (cm)/serum creatinine (mg/dL)\]0.516 × \[1.8/cystatin C\]0.294 × \[30/blood urea nitrogen\]0.169 × \[1.099\]if male × \[height(m)/1.4\]0.188. Children with missing baseline or 2 years GFR were excluded from the analysis.
Time frame: Before initiation of treatment and at 2 years
200 patients planned; 233 patients screened; 197 patients eligible for study participation; 193 patients randomized to study treatment; 191 patients initiated study treatment
| Milestone | Hydroxyurea | Placebo |
|---|---|---|
| Started | 96 | 97 |
| Completed | 83 | 84 |
| Not completed | 13 | 13 |
Primary Endpoint: Spleen function was assessed by uptake of 99mTc sulfur colloid on liver-spleen scan before initiation of treatment (baseline) and 2 years later (exit). The results of each of the two scans were categorized as normal, functional but abnormal, or not functional by a panel of nuclear medicine specialists blinded to treatment assignment. The proportion of patients whose paired scans demonstrated a decline in splenic function was compared in the hydroxyurea versus placebo groups. The change in splenic function from baseline to 2 years was defined as worse if it changed from normal to decreased or absent, or decreased to absent; and not worse if it changed from decreased to decreased, normal to normal, or decreased to normal.
| Participants | Hydroxyurea | Placebo |
|---|---|---|
| Worse | 19 | 28 |
| Not worse | 51 | 46 |
DTPA GFR was originally a co-primary efficacy outcome for the study. Later in May 29, 2009, this measurement was discontinued because of statistical futility (an extremely small chance that the difference between treatment groups would be statistically significant for this outcome) and the small risk posed by the radiation exposure involved with performing the DTPA GFR test. Subjects who had missing data at baseline or 2 years measurement were excluded from the analysis (29 subjects from the hydroxurea, and 31 subjects from the placebo group excluded).
| mL/min/1.73m^2 | Hydroxyurea | Placebo |
|---|---|---|
| Change From Baseline in the Renal Function That Was Measured by Diethylenetriaminepentaacetic Acid (DTPA) Glomerular Filtration Rate (GFR) | 22.56 ± 54.67 | 20.74 ± 51.07 |
Schwartz formula used to calculate GFR is: 0.55× height (cm)/serum creatinine (mg/dL). Where height is in cm and serum creatinine is in mg/dL. Children with missing baseline or 2 years GFR were excluded from the analysis.
| mL/min/1.73m^2 | Hydroxyurea | Placebo |
|---|---|---|
| Change From Baseline in the Renal Function That Was Measured by Glomerular Filtration Rate (GFR) (Calculated Using Schwartz Formula) | 28.65 ± 76.46 | 33.36 ± 95.85 |
GFR was calculated using new Schwartz formula: 39.1× \[height (cm)/serum creatinine (mg/dL)\]0.516 × \[1.8/cystatin C\]0.294 × \[30/blood urea nitrogen\]0.169 × \[1.099\]if male × \[height(m)/1.4\]0.188. Children with missing baseline or 2 years GFR were excluded from the analysis.
| mL/min/1.73m^2 | Hydroxyurea | Placebo |
|---|---|---|
| Change From Baseline in the Renal Function That Was Measured by GFR (Calculated Using New Schwartz Formula) | 10.57 ± 20.78 | 14.33 ± 24.01 |
Collected over From randomization through study completion, an average of 1.93 years.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Hydroxyurea | 0/96 (0%) | 19/96 (19.8%) | 95/96 (99%) |
| Placebo | 0/97 (0%) | 35/97 (36.1%) | 95/97 (97.9%) |
| Event | Hydroxyurea | Placebo |
|---|---|---|
| Acute Chest SyndromeRespiratory, thoracic and mediastinal disorders | 6/96 | 19/97 |
| Splenic SequestrationBlood and lymphatic system disorders | 11/96 | 12/97 |
| ABNORMAL TCDInvestigations | 1/96 | 3/97 |
| APLASTIC CRISISBlood and lymphatic system disorders | 0/96 | 2/97 |
| SEPSIS OR MENINGITISInfections and infestations | 0/96 | 2/97 |
| Acute chest syndromeBlood and lymphatic system disorders | 1/96 | 0/97 |
| PainGeneral disorders | 1/96 | 0/97 |
| FEVER > 101.5°F(38.4°C)General disorders | 1/96 | 0/97 |
| Possible Accidental Hydroxyurea overdoseInjury, poisoning and procedural complications | 1/96 | 0/97 |
| DVTVascular disorders | 1/96 | 0/97 |
| Event | Hydroxyurea | Placebo |
|---|---|---|
| UPPER RESPIRATORY INFECTIONInfections and infestations | 83/96 | 77/97 |
| FEVER >101.5 F (38.4 C)General disorders | 75/96 | 82/97 |
| PainGeneral disorders | 50/96 | 62/97 |
| Otitis MediaInfections and infestations | 38/96 | 48/97 |
| Viral SyndromeInfections and infestations | 46/96 | 46/97 |
| DACTYLITISMusculoskeletal and connective tissue disorders | 14/96 | 43/97 |
| SPLENOMEGALYBlood and lymphatic system disorders | 32/96 | 35/97 |
| GASTROENTERITISInfections and infestations | 33/96 | 31/97 |
| CONSTIPATIONGastrointestinal disorders | 16/96 | 33/97 |
| RashSkin and subcutaneous tissue disorders | 21/96 | 29/97 |
| Age, Categorical(Participants) | Hydroxyurea | Placebo | Total |
|---|---|---|---|
| <=18 years | 96 | 97 | 193 |
| Between 18 and 65 years | 0 | 0 | 0 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(Months) | Hydroxyurea | Placebo | Total |
|---|---|---|---|
| Mean | 13.57 ± 2.60 | 13.56 ± 2.74 | 13.56 ± 2.66 |
| Sex: Female, Male(Participants) | Hydroxyurea | Placebo | Total |
|---|---|---|---|
| Female | 52 | 57 | 109 |
| Male | 44 | 40 | 84 |
| Race (NIH/OMB)(Participants) | Hydroxyurea | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 94 | 87 | 181 |
| White | 0 | 1 | 1 |
| More than one race | 0 | 5 | 5 |
| Unknown or Not Reported | 2 | 4 | 6 |
| Region of Enrollment(participants) | Hydroxyurea | Placebo | Total |
|---|---|---|---|
| United States | 96 | 97 | 193 |
Documents are hosted by the registry — open the source record to download them.
This study is completed, as verified in Apr 2011. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
National Heart, Lung, and Blood Institute (NHLBI)