Introduction and enrollment summary

This document provides an automated summary of data entered from ELICIT. It is generated from a dataset built from the MuSIC server and is updated weekly. These data lag the actual collected data by roughly two weeks (for the primary forms) and in some cases longer (e.g. for labs that have a longer turnaround time). Also, because data quality is being monitored, with corrections made and missing data added, there can be some variance in the data from day to day even if new subjects have not been added.

As of today, inital assessment data from 1205 children have been entered (this includes 17 children who were ultimately not eligible)

The number of children with initial assessment data entered by week since enrollment began is as follows:

Eligibility

Of the 17 children who were not eligible, 3 did not consent to participation, 7 expected to move from the study area, 1 had a mother with age < 18, 2 were from a multiple pregnancy, 2 children were not healthy at the time of assessment, 0 had a child weight less than 1.5kg, 2 children were older than 14 days of age, 0 were not eligible for other reasons, and 0 already had a child enrolled in ELICIT. Additionally, 90 children did not remain in the study. 13 of these were due to death.

This leaves 1098 children in the study at present.

Modified intention to treat vs per protocol

Of the 918 children who are 18 months or older, 919 have the outcome of interest measured. Of these, 792 meet the per protocol criteria (ie breastfed for 6 month, at least 50% of nicotinamide doses, all azithromycin doses, first doses of nitazoxinide, outcome of interest measure). When restricting the per protocol definition to include only antimicrobial doses received during the approved protocol window, 446 meet the definition.

Baseline characteristics by randomization arm

Group 1 (n = 280) Group 2 (n = 278) Group 3 (n = 274) Group 4 (n = 266)
child age (days) 6 +/- 3.4 5.9 +/- 3.7 5.9 +/- 3.6 5.9 +/- 3.7
# male sex (%) 147 (52.5%) 142 (51.1%) 141 (51.5%) 137 (51.5%)
# born in hospital (%) 155 (55.4%) 148 (53.2%) 131 (47.8%) 134 (50.4%)
Median family income med:30000 (min: 5000, max: 6e+05) med:30000 (min: 5000, max: 3e+05) med:30000 (min: 5000, max: 360000) med:30000 (min: 1500, max: 3e+05)
Mother with >= 7 years of education (%) 227/280 (81.1%) 196/278 (70.5%) 203/274 (74.1%) 196/266 (73.7%)
Birth order med:3 (min: 1 max: 12) med:4 (min: 1 max: 12) med:4 (min: 1 max: 12) med:3.5 (min: 1 max: 12)
# Iraqw 218/280 (77.9%) 228/278 (82%) 217/274 (79.2%) 215/266 (80.8%)
# w/ improved sanitation (%) 37/280 (13.2%) 21/278 (7.6%) 25/274 (9.1%) 33/266 (12.4%)
# w/ improved drinking water (%) 185/280 (66.1%) 181/278 (65.1%) 187/274 (68.2%) 175/266 (65.8%)
# treating water (%) 38/280 (13.6%) 26/278 (9.4%) 32/274 (11.7%) 27/266 (10.2%)
# w/ water > 10 minute walk away (%) 230/280 (82.1%) 222/278 (79.9%) 224/274 (81.8%) 211/266 (79.3%)
# w/ electricity (%) 100/280 (35.7%) 97/278 (34.9%) 88/274 (32.1%) 87/266 (32.7%)
# w/ mattress (%) 173/280 (61.8%) 153/278 (55%) 148/274 (54%) 150/266 (56.4%)
# w/ table (%) 137/280 (48.9%) 107/278 (38.5%) 106/274 (38.7%) 105/266 (39.5%)
# w/ bench (%) 246/280 (87.9%) 236/278 (84.9%) 223/274 (81.4%) 228/266 (85.7%)
# w/ separate kitchen (%) 183/280 (65.4%) 165/278 (59.4%) 172/274 (62.8%) 158/266 (59.4%)
# w/ refrigerator (%) 5/280 (1.8%) 2/278 (0.7%) 2/274 (0.7%) 5/266 (1.9%)
# w/ television (%) 18/280 (6.4%) 16/278 (5.8%) 20/274 (7.3%) 15/266 (5.6%)
# w/ mobile phone (%) 230/280 (82.1%) 236/278 (84.9%) 222/274 (81%) 223/266 (83.8%)
# w/ family bank account (%) 22/280 (7.9%) 18/278 (6.5%) 9/274 (3.3%) 12/266 (4.5%)
# own agricultural land (%) 268/280 (95.7%) 266/278 (95.7%) 265/274 (96.7%) 256/266 (96.2%)
maternal age (years) 28.1 +/- 7.1 27.8 +/- 6.7 27.9 +/- 6.1 27.8 +/- 6.6
enrollment length (cm) 49.2 +/- 2 min:42.2 max: 59 48.8 +/- 2.1 min:40 max: 57 49.1 +/- 2.1 min:41 max: 55 49.1 +/- 2.1 min:38 max: 57
enrollment weight (kg) 3.1 +/- 0.5 min:1.8 max: 4.6 3.1 +/- 0.5 min:1.9 max: 4.7 3.1 +/- 0.5 min:1.6 max: 4.4 3.1 +/- 0.5 min:1.6 max: 5.7
enrollment head circumference (cm) 34.7 +/- 1.3 min:31.3 max: 38.2 34.6 +/- 1.3 min:30 max: 38.4 34.8 +/- 1.4 min:28.3 max: 38.5 34.8 +/- 1.3 min:31.5 max: 40

Illness, healthcare accessed, and antibiotic use

####Healthcare accessed in last week by child age and nicotinamide assignment

####Healthcare accessed in last week by child age and antibiotic assignment

####Illness in the last week by child age and nicotinamide treatment assignment:

####Illness in the last week by child age and antibiotic treatment assignment:

####Antibiotic use in the last week by child age and nicotinamide treatment assignment:

####Antibiotic use in the last week by child age and antibiotic treatment assignment:

##Adverse events in mothers To date, there have been 468 adverse events in mothers (250 in NIC-A and 218 in NIC-B). There have been 26 serious adverse events(14 in NIC-A and 12 in NIC-B) and 0 adverse events deemed related or possibily related to study medications (0 in NIC-A and 0 in NIC-B).

####Serious adverse event categories in mothers by nicotinamide arm: Events may include multiple diagnoses

Diganosis Nic-A Nic-B
ALRI 2 3
diarrhea 3 2
DVT 1 0
Lab abnormality 2 3
Other 6 6
Sepsis 2 3
Injury/Burn/Bites 1 0
Septicemia 0 1
Ear infection 0 1

The “other” serious AEs for NIC-A were as follows: EPILEPSY, UNSPECIFIED GASTROINTESTINAL ILLNESS, ACUTE ASTHMATIC ATTACK, 1. UNSPECIFIED RESPIRATORY ILLNESS, UNSPECIFIED ILLNESS, 1. ANGINA PECTORIS.

The “other” serious AEs for NIC-B were as follows: POSTPARTUM PRE ECLAMPSIA, SCHIZOAFFECTIVE DISORDER, SUSPECTED ORGANOPHOSPHATE POISONING, SEIZURE DISORDER, 1. SUSPECTED ANGINA PECTORIS, UNSPECIFIED ILLNESS

Adverse events in children

###By Nicotinamide arm: To date, there have been 4554 adverse events in children (2267 in NIC-A and 2287 in NIC-B). There have been 281 serious adverse events(134 in NIC-A and 147 in NIC-B) and 0 adverse events deemed related or possibily related to study medications (0 in NIC-A and 0 in NIC-B).

Of the 13 that died, 7 were in Nic-A, and 6 were in Nic-B.

####Serious adeverse events by nicotinimide arm for children six months and younger An adverse events may include multiple diagnoses

Diagnosis Nic-A Nic-B
Acute watery diarrhea 3 4
ALRI 39 36
diarrhea 7 12
Jaundice 0 1
Lab abnormality 7 5
Malnutrition 1 0
Sepsis 8 12
Skin rash/infection 0 1
UTI 1 1

The “other” SAEs for NIC-A were as follows:

The “other” SAEs for NIC-B were as follows:

####Serious adverse events by nicotinamide arm for children older than six months An adverse events may include multiple diagnoses

Diganosis Nic-A Nic-B
Acute watery diarrhea 3 7
ALRI 42 43
diarrhea 50 42
Dysentery 0 1
fever 2 3
Injury/Burn/Bites 1 3
Lab abnormality 20 25
Malnutrition 5 4
Omphalitis 1 0
Other 8 4
Septicemia 1 3
Skin rash/infection 1 1
UTI 0 4

The “other” serious AEs for NIC-A were as follows: 1. ADENOID HYPERTHROPHY, 1. CHICKEN POXS WITH BACTERIAL SUPERINFECTION, SUSPECTED SEXUAL ABUSE., SCORPION BITE, ACUTE BACTERIAL MENINGITIS , UNSPECIFIED GASTROINTESTINAL ILLNESS, 1. GASTRROENTERITIS WITH SOME DEHYDRATION, (1)UNSPECIFIED GASTROINTESTINAL ILLNESS(

The “other” serious AEs for NIC-B were as follows: 1. SUSPECTED BACTERIAL MENINGITIS , PNEOMONIA, UNSPECIFIED GASTROINTESTINAL ILLNESS, CHICKEN POX

###By antibiotic arm

To date, there have been 3014 adverse events in children 6 months and older, (1570 in ANTI-A and 1444 in ANTI-B). There have been 180 serious adverse events(92 in ANTI-A and 88 in ANTI-B) and 0 adverse events deemed related or possibily related to study medications (0 in ANTI-A and 0 in ANTI-B).

Of the 13 that died, 8 were in Anti-A, and 5 were in Anti-B.

####Serious adverse events for children older than 6 months An adverse events may include multiple diagnoses

Diganosis ANTI-A ANTI-B
Acute watery diarrhea 4 6
ALRI 45 40
diarrhea 44 48
Dysentery 1 0
fever 4 1
Injury/Burn/Bites 3 1
Lab abnormality 21 24
Malnutrition 6 3
Omphalitis 1 0
Other 6 6
Septicemia 2 2
Skin rash/infection 1 1
UTI 2 2

The “other” serious AEs for ANTI-A were as follows: 1. ADENOID HYPERTHROPHY, 1. CHICKEN POXS WITH BACTERIAL SUPERINFECTION, SCORPION BITE, UNSPECIFIED GASTROINTESTINAL ILLNESS, 1. GASTRROENTERITIS WITH SOME DEHYDRATION, (1)UNSPECIFIED GASTROINTESTINAL ILLNESS(

The “other” serious AEs fo ANTI-B were as follows: 1. SUSPECTED BACTERIAL MENINGITIS , PNEOMONIA, UNSPECIFIED GASTROINTESTINAL ILLNESS, SUSPECTED SEXUAL ABUSE., CHICKEN POX, ACUTE BACTERIAL MENINGITIS

##By randomization arm

All serious adverse events for children older than 6 months An adverse events may include multiple diagnoses

Protocol deviations by nicotanmide arm

NIC-A NIC-B
Any protocol deviation 528 460
Inappropriate documentation of consent 0 1
Study medication given outside of time window 174 168
Study antimicrobials given prior to stool colelction 5 2
Incorrect does of study medication 0 1
Delay of AE/SAE reporting 4 4
Blood for safety labs at 2 months (first 100 participants) not obtained 345 284

Protocol deviations by antibiotic arm

ANTI-A ANTI-B
Any protocol deviation 527 461
Inappropriate documentation of consent 0 1
Study medication given outside of time window 177 165
Study antimicrobials given prior to stool colelction 4 3
Incorrect does of study medication 1 0
Delay of AE/SAE reporting 1 7
Blood for safety labs at 2 months (first 100 participants) not obtained 344 285

##Protocol deviations by study arm

1 2 3 4
Any protocol deviation 297 231 230 230
Inappropriate documentation of consent 0 0 0 1
Study medication given outside of time window 96 78 81 87
Study antimicrobials given prior to stool colelction 3 2 1 1
Incorrect does of study medication 0 0 1 0
Delay of AE/SAE reporting 0 4 1 3
Blood for safety labs at 2 months (first 100 participants) not obtained 198 147 146 138

Compliance with study medications

Objective nicotanimide pill/packet compliance (based on pill/packet counting performed every 2 months starting at the 2 month visit):

Subjective nicotanimide pill compliance (based on maternal report of pills consumed in the previous 7 days at each monthly visit):

Subjective nicotinimide packet compliance based on maternal report of the number of packets missed in the last 7 days

##Objective compliance vs subjective compliance

Subjective minority Subjective majority
Objective minority 105 1001
Objective majority 286 7305

Breastfeeding status

####Prevalence of breastfeeding as primary source of food by child age in months and nicotinamide treatment assignment: