Table 3.
Safety Outcomes during the 13-Week Trial Period.*
| Event | Bionic Pancreas (N = 219) |
Standard Care (N = 107) |
P Value† |
|---|---|---|---|
| Any adverse event‡ | |||
| No. of participants with event (%) | 126 (58) | 8 (7) | — |
| No. of events | 244 | 10 | |
| Severe hypoglycemia§ | |||
| No. of participants with event (%) | 10 (5) | 2 (2) | 0.39 |
| No. of events | 10 | 3 | |
| Incidence rate per 100 participant-yr | 17.7 | 10.8 | |
| Diabetic ketoacidosis — no. of events¶ | 0 | 0 | ND |
| Other serious adverse event∥ | |||
| No. of participants (%) | 3 (1) | 2 (2) | 0.77 |
| No. of events | 3 | 2 | |
| Incidence rate per 100 participant-yr | 5.3 | 7.2 | |
| Increase in the glycated hemoglobin level by ≥0.5 percentage points — no. of participants (%) | 17 (8) | 8 (7) | 0.74 |
| Hyperglycemia with or without ketosis related to trial device** | |||
| No. of participants with event (%) | 95 (43) | NA | — |
| No. of events | 160 | NA | |
| Hyperglycemia with or without ketosis not related to trial device | |||
| No. of participants with event (%) | 44 (20) | 1 (1) | — |
| No. of events | 54 | 2 | |
| Nonsevere hypoglycemia | |||
| No. of participants with event (%) | 2 (1) | 0 | — |
| No. of events | 2 | 0 | |
| Other reportable adverse events | |||
| No. of participants with event (%) | 14 (6) | 3 (3) | — |
| No. of events | 15 | 3 |
NA denotes not applicable, and ND not done (according to the statistical analysis plan).
P values were calculated only for the outcomes that were prespecified in the statistical analysis plan. The P value for the number of severe hypoglycemic events per participant was produced from a Poisson regression model with adjustment for age at randomization, the glycated hemoglobin level as assessed by the central laboratory at randomization, the occurrence of at least one event of severe hypoglycemia before randomization, and site (random effect). A P value for the number of other serious adverse events per participant was produced from a Poisson regression model with adjustment for age at randomization, the glycated hemoglobin level as assessed by the central laboratory at randomization, and site (random effect). The P value for the percentage of participants with a glycated hemoglobin level that increased by at least 0.5 percentage points was produced from a marginal logistic-regression model with adjustment for age at randomization and the glycated hemoglobin level as assessed by the central laboratory at randomization, with a compound symmetry covariance structure to handle the correlated outcomes within site.
Reportable adverse events as defined in the protocol included the following: serious adverse event; adverse device effect (i.e., an adverse event related to use of a trial device); adverse event occurring in association with a trial procedure; adverse event not related to a device issue that led to temporary or permanent discontinuation of a trial device; adverse event for which a visit was made to the emergency department; severe hypoglycemia with cognitive impairment requiring the assistance of a third party for treatment; diabetic ketoacidosis; and hyperglycemic or ketosis event for which a visit occurred, a health care provider was contacted, or the blood ketone level was at least 1.0 mmol per liter.
Among participants 18 years of age or older, seven events of severe hypoglycemia occurred in seven participants (6.5%) in the bionic-pancreas group and two events in one participant (1.9%) in the standard-care group (incidence rate per 100 participant-years, 25.5 vs. 14.2; P = 0.40). Among participants younger than 18 years of age, three events of severe hypoglycemia occurred in three participants (2.7%) in the bionic-pancreas group and one event in one participant (1.9%) in the standard-care group (incidence rate per 100 participant-years, 10.4 vs. 7.3).
In the group of 114 participants using the bionic pancreas with fast-acting insulin aspart (for which data are not otherwise reported in this article), diabetic ketoacidosis occurred in 2 participants (2%) (on the basis of device evaluation, both events were considered by the medical monitor to be caused by an infusion-set failure) and severe hypoglycemia occurred in 3 (3%; incidence rate per 100 participant-years, 10.2).4
In the bionic-pancreas group, attempted suicide occurred in two participants and hypoglycemia in one. In the standard-care group, spontaneous pneumothorax and epiglottitis occurred in one participant each. The hypoglycemic event did not meet criteria for severe hypoglycemia related to cognitive impairment but was considered to be a serious adverse event (clinically significant medical event) as judged by the investigator.
The trial device included the insulin pump, infusion set, and continuous glucose monitor. Most adverse events of hyperglycemia that were considered to be related to the trial device were due to infusion-set failures.